#1

&PROANALYST&2 - QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIPS (QSAR) IN
PROTEINS, PROTEIN ENGINEERING, PATTERNS RECOGNITION IN COMBINATORIAL
LIBRARIES, PHYSICO-CHEMICAL AND ALPHABETICAL ANALYSIS FOR MULTIPLE
            SEQUENCE ALIGNMENTS AND 3D STRUCTURE

			   DEMO VERSION

     COPYRIGHT (C) 1996 Vladimir A.Ivanisenko, Alexey M.Eroshkin

  Theoretical Dept., Research Institute of Molecular Biology,
  SRC VB "Vector", 633159, Koltsovo, Novosibirsk region, Russia

  Tel. (3822) 647774
  Telex 133196 NPO SU
  Fax: (3832) 328831;
  E.mail: salex@vector.nsk.su, eroshkin@vector.nsk.su

PRESS ENTER TO CONTINUE
#2
MAIN MENU
To start the program you have to switch your current directory to the one
which contains all necessary files (see &General information&30), and
type PROANALY.EXE and press Enter.  On the screen you'll see the main menu:

&File&21  &Options&22  &Prepr data&23  &Analysis&24  &View 3D-st&25 &Help &26

&Quit&27

Right and left arrow keys change highlighted options of menu (the
description of each them is shown simultaneously on bottom line of the
screen). When <Enter> is pressed the menu's highlighted option is
selected. You can enter to the sections: "Analysis" only after execution
of options "File", "Protein" and "Prepare data"; "View 3D-structure" only
after execution of options "File" and "Load 3D-structure".

#21 - File -

When "File" item of the main menu is selected the following submenu
appears:
Ŀ
                     
 &Property      &211      
 &Load Protein  &212      
 &Load 3D-struct&213      
 &Result        &214      
 &Save Protein  &215      
 &Prot from 3D  &800      
 &Commander     &216      

You can enter to the sections: "Save protein" only after execution of
options "File", "Protein" and "Prepare data".   &Main menu&2

#22
- Options -
In this option user gets the following menu to input parameters
for further calculations:
   Ŀ
       &Calculation&221                             
       &Sequences display mode&222                  
       &Display residues exposure (on/off)&223      
       &Display 2D structure (on/off)&224           
       &Display protein name (on/off)&225           
       &Display activity (on/off)&226               
       &View marked fragments (Current/All)&227     
       &Window for protein name&228                 
       &Window for activities&229                   
       &Window for graphics&805                     
       &Show property on a screen&2210               
       &Sorting by (increase/decrees)&9211           
                                               
   
Each parameter has some default value.
&Main menu&2
#23
-Prepare data-

This is one of the two main program units.  User can enter to this unit
only after correct choosing of data in units &File&21 and &Load Protein&212.
Entering to "Prepare Data" user will get the window with aligned amino
acid sequences of investigated protein/peptide family.

In upper line of the window it is shown:

Line, Col - positions of cursor in the multiple
            aligned sequences,
Grp - the number of current active group
      (number of groups is less than 9),
Frg - the number of current active fragment (number of
      fragments is less than 9),
Ppt - value of a physico-chemical property of amino acid under cursor.

Keys <Alt B> and <Alt E> are used to mark the fragment for analysis.
Keys <Alt 1>, ...  , <Alt 8> are used to change the current fragment
number.  Keys <Ctrl Alt 1>, ...  , <Ctrl Alt 8> are used to change the
current active group of proteins.  Keys <Ctrl Alt I> are used to combine
all proteins to one group (with current group number).  Keys <Ctrl Alt C>
are used to exclude protein(s) from analysis or to clear current
grouping.  Such proteins will be marked with group number 0 (that is not
used in analysis but in predictions only).  The proteins having group
number equal to zero are not used in calculations. To change group number
press ENTER.  There are several special command keys which facilitate the
investigation of the protein family.  Keys <Alt S> are used for
&sort&247.

  Command keys          Effect

   < Esc >  Returns to the Main menu.
   < Left > Moves cursor on one position to  the  left.
   < Right> Moves cursor on one position to the right.
   < Up >   Moves the string up.
   < PgUp > Page up.
   < PgDn > Page down.
   < Down > Moves the string down.
   < Home > Moves cursor to the position of first position on the
            window.
   < End >  Moves cursor to the position of end position on the
            window.
< Ctrl Home > Moves cursor to the position of first position on
              the sequence.
< Ctrl End> Moves cursor to the position of end position on the
            sequence.
   < Alt N >            Moves to the window for editing protein names.
   < Alt D >            Moves to the window for editing protein activities
<Alt 1> ,...,  <Alt 8>  Switch between fragments. User may define up to 8
                        different regions in a protein family  (fragments
                        are  marked  by red color).  Initially the number
                        of current fragment is equal to 1.
< Alt B > , < Alt E >   Define the beginning and the end of a fragment
   < Alt U >            Unmark current fragment.
   < Alt C >            Unmark all selected fragments.
    < F7 >              Find a string (word) in a sequence under the
                        cursor.  The matrix of amino acid similarity is
                        used in the search (user choose the matrix from
                        the set).  For undefined positions symbol x
                        should be used.
    < F8 >              Invert size of letters in sequences.
    < F9 >              Clear marked motifs in sequence.

ACDEFGHIKLMNPQRSTVWY    Edit the sequence of protein (to provide protein-
                        engineering experiment, for example).

The window for protein names editing has the following command keys:

  Command keys          Effect

   < Esc >              Return to work window of proteins.
   < Left >             Moves cursor on one position to the left.
   < Right >            Moves cursor on one position to the right.
   < Up >               Moves the string up.
   < Down >             Moves the string down.
   < Home >             Moves cursor to the position of  first
                        character  on  the name.
   < End >              Moves cursor to the position of
                        end character on the name.
   < F4 >               Edit.

The window for protein activities editing has the following command keys:

  Command keys          Effect

   < Esc >              Return to work window of proteins.
   < Up >               Moves the string up.
   < Down >             Moves the string down.
   < F4 >               Edit.

   &Main menu&2
#24
- Analysis -

&Main menu&2
      In this option the user get the following menu:

 Ŀ
    &Factors definition&241         
 Ĵ
    &Structure-Activity&242         
    &Functional center &243         
    &Motifs Search     &2428         
 Ĵ
    &Profile analysis  &244         
 Ĵ
    &Save last result  &248         
    &View last result  &249         
 

The comparison of sequences in all methods of alphabetical analysis can
be done with the using of matrices of amino acid similarity (MDM78,
minimal mutational distance, etc). For physico-chemical profiles and
structure-activity analysis the factors should be determined before the
calculations.
#25
- View 3D-structure -

      In this option the user get the following menu:

  Ŀ
     &SPATIAL SITE  &251       
     &SIMPLE MARKING&252       
                          
  
#26@
- Help -
This  is  a  short  abstract
on  system  PROANALYST.  In each
submenu help information can be
invoked by pushing ENTER key.
Help information about functioning
of the  system  is  available.  In
addition, the last line of screen
lists short help for each menu
option (submenu).
#27@
- Quit -

This is exit from the program.
#30
- GENERAL INFORMATION -

                   GENERAL INFORMATION

The distribution diskette contains the following several necessary and
supplementary files.  All files should be in the same directory.  There
are files with the examples.

                    REQUIREMENTS

PROANALYST runs on the IBM PC family of computers, including XT, AT.
PROANALYST requires DOS 3.3 or higher and at least 500K of RAM; it will
run on any 80-column monitor but graphics require EGA/VGA monitor.  A
hard disk is recommended for enhancing performance of the program.


                  STANDARD ERRORS LIST

ERROR=0 - successful finishing the program.

In case of some problems the program sends the following messages:

ERROR= -1 - file input/output error.  The program can not find the file
with the given filename.  Recommendation: check the filename and correct
it.

ERROR= -2 - there is not enough RAM (random access memory) in your
computer to execute the program.  Recommendations: unload resident
programs, use high memory or divide your protein sequences into two
overlapping parts and investigate them separately.

ERROR= -79 - errors in datafiles: 1.  The number of sequences is not
equaled to the number of data in activity file. 2.  There are lines
without data in the file with activities.  Recommendation: check the file
with activities and correct it (in case if activity is not known for any
member of the family, input some number like 9999, but do not use this
protein in structure-activity).


                    NOTE FROM AUTHORS

The program is constantly growing, so the manual may have some slight
differences with the current state of the program.

If you've found errors or have any proposals to improve PROANALYST
program please contact Ivanisenko V.A. or Eroshkin A.M., Research
Institute of the Molecular Biology, SRC VB "Vector", Koltsovo,
Novosibirsk region, 633159, Russia.

Tel.(3832)-64-77-74
Telex 133196 NPOSU
Fax: (3832) - 328831;
E.mail: salex@vector.nsk.su  (to Vladimir Ivanisenko),
eroshkin@vector.nsk.su (to Alexey Eroshkin)


FEEL FREE TO CALL US. We'll be very glad to hear from you anyway.

&Main menu&2
#221
- Calculation -

 Ŀ
  &Analysis based on           &2211       
  &Function 1D-structure       &2212       
  &Function 3D-structure       &2213       
  &Hypotheses amount           &2214       
  &Min frame                   &2215       
  &Max frame                   &2215       
  &Gaps treatment              &2218       
  &Fragments                   &2219       
  &Min number evaluate factors &22110       
  &Max number evaluate factors &22110       
  &Cutoff radius               &22112       
  &Type of input atoms         &22113       
  &Profile smoothing           &22114       
 

Go to  &Main menu&2

#2212
- Function 1D-structure -

In this program we took into account 10 possible ways of fragment
characteristic calculation from its amino acid sequence or composition:

  Ŀ
   Average for a fragment                     (on/off) 
   Moment, Alpha-helix periodicity            (on/off) 
   Moment, Pi-helix periodicity               (on/off) 
   Moment, Beta-strand flat periodicity       (on/off) 
   Moment, Beta-strand twist periodicity      (on/off) 
   Moment, 3-10-helix periodicity             (on/off) 
   Minimum value for a fragment               (on/off) 
   Maximum value for a fragment               (on/off) 
   Amplitude value for a fragment (max - min) (on/off) 
   Sum for a fragment                         (on/off) 
  

User can switch on or off each type of function.  5 modes of moment
calculation are introduced - each of them is connected with a different
type of secondary structure of the region (Schultz and Schirmer, 1979).
These characteristics are calculated by the same formula (Eisenberg et
al., 1984) and differ only by values of periodicity angles (or by number
of amino acid residues per turn).  In this section user switches off or
on some particular function for calculation of the fragment
characteristic; the way how to process gaps.

&Main menu&2
#2213
- Function 3D-structure -
This option is available when option "Analysis based on - 3D structure"
is chosen.  With the using of protein 3D coordinates the all neighbors
for each amino acid residue are defined (via some threshold distance
between C- alpha or C-beta or all atoms).  Then this amino acid residues
are considered as spatial site.  For this spatial site the following
characteristics can be calculated:
Ŀ
 Average for a spatial site                     (on/off) 
 Minimum value for a spatial site               (on/off) 
 Maximum value for a spatial site               (on/off) 
 Amplitude value (max - min) for a spatial site (on/off) 
 Sum for a spatial site                         (on/off) 
 Dipole moment for a spatial site               (on/off) 
 Empirical potential energy for ss              (on/off) 
 Short range potential energy for ss            (on/off) 
 Long range potential energy for ss             (on/off) 
 Disp of L-r potential energy for ss            (on/off) 
 Mean of L-r potential energy for ss            (on/off) 


Dipole moment for a spatial site is calculated for each physical and
chemical properties that are loaded.

Empirical potential energy calculations are defined by algorithm of
Crippen (G.M Crippen and V.N. Viswanadhan. 1984). The empirical potential
energy consists of two terms: short-range and long-range energies.

Dispersion and mean value of long-range potential energies are
calculated for 6 protein sites tertiary structures, obtained as the
result of variations in amino acid residues (Ca-atoms) coordinates of
initial site.  Modified Ca-atoms coordinates are calculated as initial
coordinates +/- 1 angstrom relative to axes X, Y and Z.  The long-range
potential energy is calculated for each new site structure. Then
the dispersion and mean value of long-range potential energies for 6
varied structures are calculated.
User  can  switch  on or off each type of function.

  &Main menu&2
#222
- SEQUENCES DISPLAY MODE. -

One of the two types of displaying protein sequences on the screen may be
used: "sequence" and "change".  If "sequence" mode is selected then
complete sequences are displayed.  If "change" mode is selected then only
amino acid differences are displayed for second, third, fourth, etc.
sequences relative to the first sequence.  Default value is: CHANGE.

&Main menu&2
#223
DISPLAY RESIDUES EXPOSURE

The surface amino acid residues will be shown in green if the mode "ON"
is chosen (and if the relative file *.exp exists). Default value is: ON.

&Main menu&2

#224
- Display 2D-structure. -


The protein 2D structure will be shown above the sequences in the
mode ON is chosen (and if the relative file *.exp exists).
Default value is: ON.


&Main menu&2
#225
DISPLAY PROTEIN NAME

The names of proteins are displayed on the screen in case ON.
Default value is: ON.

&Main menu&2
#226@
DISPLAY ACTIVITY

The activities of proteins
are displayed on the screen
in case On.  Default value
is: ON.
#227@
VIEW MARKED FRAGMENTS

There are two modes of
working:

1.CURRENT - only current
fragment will be marked in
red.

2.ALL - all selected
fragments will be marked in
red.

Default value is: CURRENT.
#228@
- Width window for name sequence. -

Size of windows for protein name.
Default value is 15.
#229@
- Width window for activities -

Size of windows for protein activities.
Default value is 5.
#805
- Window for graphics -

Sizes of window for graphs (structure-activity, profiles, discriminant
function) can be changed in this option.

Left - the coordinate of the left side of the window on the screen
(min value is 1, max value is 80). Default value is 6.

Top - the coordinate of the top side of the window on the screen
(min value is 1, max value is 25). Default value is 5.

Right - the coordinate of the right side of the window on the screen
(min value is 1, max value is 80). Default value is 74.

Down - the coordinate of the down side of the window on the screen
(min value is 1, max value is 25). Default value is 20.

#2210@
SHOW PROPERTY ON A SCREEN

User can choose amino acid property to
show property on a screen.  Default
value is: first property in the list.
#9211
SORTING BY

There are two ways of protein sorting in the set:

1.  INCREASE - to sort by increasing protein activities or group numbers.

2.  DECREASE - to sort by decreasing protein activities or group numbers.

Default value is: DECREASE.

To sort the protein set press "Alt S" in the main program window
and select appropriate mode of sorting.

#241
Factors definition

Here user inputs the set of factors that will be used in calculations of
regression, discriminant and profile analysis.  The factor is the
combination of three parameters: fragment of sequence, function and
physico-chemical property.  To select the factors it is necessary to go
through the set of menus.  At first it is necessary to select the
fragment (from the set of fragments inputted in section
&PREPARE_DATA&23).  Then the user selects the function(s) to calculate
site characteristics.  Then the user selects the physico-chemical
property(ies) to calculate site characteristics.  All marked
physico-chemical property(ies) will be used in calculations with the
earlier chosen functions.  To move through the menu use the keys: End,
Home, PgUp, PgDn, Up, Down.

  Command keys          Effect

   < Enter >            Choosing of fragment, function or property.
   < Esc >              Return to previous menu.
   < F1 >               Help
&Main menu&2

#242
- Structure-Activity -

The analysis of relationship between structure and activity in a family
of proteins/peptides is performed in this section.

  Ŀ
    &Multiple linear regression analysis&2421        
    &Discriminant analysis              &2422        
    &Cross groups variation             &2423        
  

Section serves for calculation of relations between protein activities
and structural characteristics of spatial or sequences sites and
searching for activity modulating centers.  It is necessary to define
factors (see &Factors definition &241) for multiple linear regression and
discriminant analysis.  For methods Cross groups variation it is necessary
to select fragments only (see &PREPARE_DATA&23).

After selection type of the analysis menu "Automatic" "Hand" will be
shown.


  Command keys          Effect

   < Esc >              Abort.
   < Enter >            Start of the analysis.

           Analysis in Automatic and Manual (by hand) modes.

In automatic mode the program generates and verifies hypotheses on the
location of a sequential activity-modulating region in a protein, and key
characteristics of this region.  The search depends of the values of
MIN FRAME and MAX FRAME as well as of the types and numbers of selected
factors (&Factors definition&241).  The window with the results appears by
the end of automatic.  The results are ranked set of best hypotheses
on structure-activity relation.  User can mark one hypotheses for
further analysis in the manual mode (BY HAND).  Remember, that after
marking some hypothesis the set of initially selected factors will be
replaced by factors from marked hypothesis.

#2421
Multiple linear regression analysis

Multiple linear regression permits to estimate the correlations
(dependencies) between the variables and activity and to verify
hypothesis on the nature of activity-modulating centers.  Such centers
can include different parts of protein structure (discrete centers) or
can have more than one key amino acid property influencing protein
activity (e.g. charge and volume).

The window with the results of automatic search can be shown in
submenu &VIEW LAST RESULT&249.

In this unit the following characteristics are shown:
 - site: property: function;
 - the regression equation;
 - 0.95 confidence intervals for all parameters of regression;
 - all test statistics and their confidence levels;
 - multiple correlation coefficient;
 - coefficient of multiple determination;
 - total variance of activity;
 - residual mean square error (RMSE);

To visualize the results of multiple regression analysis the graphs of
projections and correlation line between theoretical and measured
activities are used (press F5 and F6 keys in the window with the textual
results).

The projection is regression line for one factor when other factors are
fixed (mean values is putting to regression equation for fixed factors).

  Command keys          Effect

   < Esc >              Abort.
   < F2 >               Writes the results to the disk.
   < F5 >               Plot structure-activity graphs.
                        Press F2 in this window to print the
                        screen on laser or matrix printer.
   < F6 >               Correlation line between theoretical and
                        measured activities.


#2422
Discriminant analysis

Discriminant analysis is used in the cases when protein activities are
given only qualitatively or when protein are divided into groups by
some criteria (Klecka, 1986).  It is possible to define the site and
physico-chemical factor describing the given protein partition with the
using of this analysis.  Obtained coefficients of canonical discriminant
functions can be used in further classification of proteins.

At first, the proteins should be divided in two or more groups.  Then
the proteins should be sorted in order of increasing group numbers
(press "Alt S" and select "SORT BY GROUPS").

The window with the results of automatic search can be shown in
submenu &VIEW LAST RESULT&249.

   The results of discriminant analysis have a lot of information:
1. Eigenvalues.
2. Ratio of eigenvalues to their sum.
3. Canonical correlation (R) %.
4. Square of canonical correlation (R^2) %.
5. Lambda-statistic of Wilks S.S.
  5.1 Number of functions (k).
  5.2 The values of statistics.
  5.3 Statistics Chi-square  (degrees of freedom and critical values for
      95% and 99% confidence level).
6. Discriminant function coefficients.
7. Standardized coefficients.
8. Structural coefficients (Pearson's correlation coefficients).

   This window has the following command keys:

  Command keys          Effect

   < Esc >              Abort.
   < F5 >               Plot graph of discriminant function.
   < F2 >               Writes the results to the disk.
   < F5 >               Plot graphics. Use F2 in this window to
                        prints the screen on laser or matrix printer.
   < Enter >            Calculation  for the next factor combination.
#2423
Cross groups variation

At the first stage of finding an activity-modulating regions the
alphabetical analysis is reasonably to use.  Let us divide protein
family into N groups of proteins with similar activities.  To calculate
the inter group variability index the comparison of protein sites
(sequential or spatial) can be done.  The number of protein pairs (each
from different groups) that have the same contest of amino acid residues
in given site is calculated at the first step.  Then this number is
divided to the common number of all possible pairs of proteins.  So we
get the number (varying from 0 to 1) that characterize the site
variability.

The estimation of variability indexes is calculated based on pairwise
comparison of proteins from different groups.

              I=1-log[9*Sum    Ri /N +1],
                        i=1,N

              Ri=  Mul    r   ,     where:
                         ij
                  j=1,M

 N - the number of protein pares,
 M - the number of position in site,
 r  - the element of matrix of similarity between aa.
  ij
Mul    - multiplication.
If r   vary in the interval [0,1] then the values for I lie in interval
    ij
[0,1]. If position is conservative, I=0.
    The following matrices are implemented in the program:
ONE - uniform matrix,
MACLACL - physico-chemical matrix of McLachlan,
MDM78  - Dyhoff's matrix for detection of distant protein relations,
ESAB - matrix of closely related aa.

  Command keys          Effect

   < Esc >              Abort.
   < F2 >               Writes the result to the disk.
   < Enter >            Next site.
#2424
Variation in current group.

The algorithms to profiles calculation are the same as in
&CROSS GROUPS VARIATION&2423 with the only difference that sites are
moving windows in protein structure (1D or 3D).  When MAX FRAME > MIN
FRAME the profile is the average for several calculated profiles with the
set of windows (lengths varying from MIN FRAME to MAX FRAME).  Entering
this section user need to select the matrix of aa similarity (from
suggested catalog of names).

#2428
Motifs search

This menu item serves to find common motifs in current group of sequences
(in the fragment No 1). Minimal and maximal lengths of searching motifs
should be defined earlier in menu item Options (Min frame, Max frame).
Length of motif is limited by 40.  The results of searching save in the
table that can be seen menu item View last result. The table has the
motif frequency (number of proteins from the current group possessing
with this motif) and sequence.  Frequent motifs, that present in the most
of the sequences are placed in the upper part of the table.  Variable
positions are shown by symbol "-".

#243
- Functional center -

Amino acid conservation in current group is calculated by the same way
as in &CROSS GROUP VARIATION&2423 procedure but pairs of
proteins are taken from the current group. The regions with low
variability indexes are considered as conservative.

The window with the results of automatic search can be shown in
submenu &VIEW LAST RESULT&249.

#244
- Profile analysis -

There are two types of profile analysis.

   Ŀ
     &Phys-chem profiles&815          
     &Alphabetical analysis&816       
   
The profile for primary structure is build with the using of sliding
window (investigated site) of 1, 2, 3, 4 and so on amino acids.  In
the case of tertiary structure profiles the procedure is as follows.
With the using of protein 3D coordinates the all neighbors for each
amino acid residue are defined (via some threshold distance between
C-alpha or C-beta atoms).  Then this amino acid residues are
considered as spatial activity-modulating site.  Spatial profile is
the result of the consequence calculation of earlier described
characteristics for all spatial sites.

#815
PHYSICO-CHEMICAL PROFILES

You can see such menu:

  Ŀ
    Average profile                
    Min profile                    
    Max profile                    
    Dispersions profile            
  Ĵ
    &View profile           on 3D&817   
    &Save profile                &818   
  

AVERAGE PROFILE
Physico-chemical or structural profiles are calculated for all
individual proteins (with the exception of proteins with group number
0).  The resulting average profile is calculated as average value (in
each point) of all profiles.

MIN PROFILE
In this case the resulting profile is equal to minimal value (not
average) in each point.

MAX PROFILE
In this case the resulting profile is equal to maximal value in each
point.

DISPERSIONS PROFILE
In this case the resulting profile is equal to variance of values in each
point.


#816
Alphabetical analysis

The methods for 3D have the same sense as in case of sequences (1D).

 Ŀ
   &Cross groups variation               1D&2423  
   &Variation in current group           1D&2424  
   &SADC-profile                         1D&820  
   &Residual Dispersion                  3D&821  
   &SADC-profile                         3D&820  
   &Cross groups variation               3D&2423  
   &Variation in current group           3D&2424  
   &Normalized cross groups variation    3D&822  
   &Coordinated changes                  3D&823  
   &Number of coordinated position       3D&823  
 Ĵ
   &View profile on           3D structure&817   
   &Save profile                          &818   
 


When MAX FRAME > MIN FRAME the profile is the average for calculations
with the set of windows with the lengths varying from MIN FRAME to MAX
FRAME.  After entering to any section user need to select the matrix of
aa similarity (from suggested catalog of names).

#820
SADC-PROFILE

For calculation of CADC-profile the proteins are divided to the some
groups with the same amino acid content in the given site (sequential
or spatial).  The variations of protein activities are calculated for
each of the groups.  The variation is the sum square of difference
between average activity for the group and the activities of each item.
Then the sum of obtained variations is calculated and divided by the
common variation of the whole protein set.

Structure-activity determination coefficient (SADC) profile based on
amino acid comparison in alphabetical analysis. SADC profile can be done
with the using of matrices of amino acid similarity (MDM78, minimal
mutational distance, etc).  After entering to this section user need to
select the matrix of aa similarity (from suggested catalog of names).
Then it is necessary to input the threshold value for estimation of site
similarity.

  Command keys          Effect

   < Esc >              Abort.
   < F5 >               Print screen.

#821
Residual Dispersion

This parameter is residual dispersion of activities after separation of
proteins on some groups.  The procedure of calculation of statistic
Residual Dispersion is taken from (W.R. Klecka, 1986).  Briefly, the
proteins are divided to the some groups with the same amino acid
content in the given site (sequential or spatial). The matrix of amino
acid similarity is used in calculations.


#822
NORMALIZED CROSS GROUPS VARIATION 3D

Normalized cross groups variation (used only for 3D sites) is equaled to
cross group variation (calculated as described earlier) multiplied by
average value of intra group conservation indexes. The last parameter,
intra group conservation index, is defined as 1 minus variability index.

#823
COORDINATED CHANGES 3D

The values of the profile are the maximal correlation coefficient (in %)
between mutations in given position and mutations in neighborhood
positions of 3D structure (Sander, 1994).  The high correlation
coefficient reflects the existing another positions (close in 3D
structure to the first) with coordinated changes.

Example of coordinated changes:
M  D
F  R
F  R
C  A
C  A

All positions within spatial site are tested for presence of coordinated
changes with the center of the site.

NUMBER OF COORDINATED POSITION 3D

The number of coordinated positions with the correlation coefficient
higher the cutoff parameter is calculated.  The correlation is
calculated based on the algorithm, described in the previous section.

#817
VIEW PROFILE ON 3D STRUCTURE

Each profile calculated in this program can be displayed on protein 3D
structure. User need to input two numbers to differentiate amino acid
residues of the protein into three sets: one set - positions with high
values on the profile, second set - positions with low values on the
profile, third set - positions with intermediate values on the profile.
Then user can see protein 3D structure with three above mentioned amino
acid residues types marked by various colors (and lines width). It is
possible to define also only two sets of positions (for example to
discriminate only high profile values on the profile).

User can change easy the modes of protein display
(see &SPATIAL SITE&251).


#818
SAVE PROFILE

In this submenu user can save to the disc any of calculated profiles.

  Command keys          Effect

   < Esc >              Abort.
   < F3 >               View file from the catalog.
   < F4 >               Editing the file.
   < F9 >               New mask.
   < New name >         Type new name in command line to save profile
                        to new file, in another case the profile will be
                        added to existing file (filename shown green)..
   < Enter >            Save profile.


&Main menu&2
#245@
- Peculiarity structure-function. -

 To be realized later.
#246@
- Set vector data. -

 To be realized later.
#247
- Sort -

To sort the protein set press "Alt S" in the main program window
and select appropriate mode of sorting.

 By activity - sorting by protein activity,
 By groups   - sorting by protein group number,
 By motifs   - sorting by motifs number in the sequence.

Choose what you need, then press ENTER and return back.  You'll get
reordered list of proteins in multiple alignment.  Sorting by protein
group numbers is absolutely necessary step if you are preparing to
provide discriminant analysis.

#248
- Save last result.-

Any result found in automatic mode can saved to the disc in this
submenu item (the file also may be edited here).

  Command keys          Effect

   < Esc >              Abort.
   < F3 >               View file from the catalog.
   < F4 >               Editing the file.
   < F9 >               New mask.
   < New name >         Type new name in command line to save result
                        to new file, in another case the result will be
                        added to existing file (filename shown green)..
   < Enter >            Save result.

&Main menu&2
#249
- View last result. -

View the result found in automatic mode. The result is shown as
short table. Each line has brief description of the result of one
calculation (one hypothesis). To see detailed result description move
cursor to desired line and press F3. Then you can see also relative
graph, if available. Also user can mark (press ENTER) one hypothesis
for further investigation in a manual mode ("by hand").  After
choosing a hypothesis the set of initially selected factors (marked
site(s), amino acid factors and functions, ( &Factors definition.&241))
will be replaced by site(s) and factors from selected hypothesis.
Then user can analyze taken factors BY HAND (in manual mode).  The
window with the results of automatic search can be shown in any
time.


&Main menu&2
#211
- Property -

This menu item lists the files containing physico-chemical properties of
amino acids (*.ppt).  After the file is selected, the program displays
the list of all properties available in this file. And user can choose
any subset of these properties.  Every file can contain up to 50
different properties.  The data in this file are organized according to
the following format:

  Comments (any number of lines started with space symbol)

  Property name (no spaces are allowed at the beginning of the name)

  Literature reference (the same requirement as above)

  Values of amino acid properties,  7 positions per one value (with space
  in 1-st position)

  The order of values should correspond to the following order of amino
  acids ACDEFGHIKLMNPQRSTVWY.

For example:

 Any comments must have a leading space
 { Property names (from 1-st position of string)
   Literature source (from 1-st position of string)
   Values of amino acid properties }

Hydrophilicity Hopp-Woods
T.P.Hopp, K.R.Woods, PNAS 78 (1981) 3824
   -.5   -1.0    3.0    3.0   -2.5    0.0    -.5   -1.8    3.0   -1.8
  -1.3     .2    0.0     .2    3.0     .3    -.4   -1.5   -3.4   -2.3
Hydropathy Kyte-Doolittle
J.Kyte, R.F.Doolittle J.Mol.Biol 157 (1982) 105
   1.8    2.5   -3.5   -3.5    2.8    -.4   -3.2    4.5   -3.9    3.8
   1.9   -3.5   -1.6   -3.5   -4.5    -.8    -.7    4.2    -.9   -1.3

You  could  also  select  any  subset  of  properties for the analysis or
prepare your own set of properties.  There are several hot keys.

  Command keys          Effect

   < Esc >              Return back.
   < Up >               Moves the cursor one position up.
   < Down >             Moves the cursor one line down.
   < Enter >            Selects/cancels selection of a property for
                        inclusion in the data set.
   < Alt I >            Selects all property from a given file.
   < Alt C >            Cancels selection of all properties that
                        were chosen earlier.
#212
- Load Protein -

Here user can select protein/peptide family to be analyzed. The
data are supposed to be prepared in three separate files:

1) File of protein names (with extension *.seq).  The format of the file
corresponds to the one of protein sequence database SWISS-PROT.  All
lines except DE (name of a protein) and // (the end of the data for a
protein) are ignored.

For example:

DE  INTERFERON ALPHA 2
//
DE  INTERFERON ALPHA 1
OS  HOMO SAPIENCE
//
....

2) File of aligned protein sequences (with extension *.ali) in one-letter
code.  The format of the file is as follows: first line - the length of
aligned amino acid sequences (after special words "Seq.file ").  Then
protein sequences - one sequence per one line (even in the case of long
sequences).  NO ADDITIONAL SYMBOLS LIKE " " (BLANK) IN THE END OF THE
LINES.  Gaps are coded by symbol '-'.  Add one or more blank lines at the
end of the file.

For example:

Seq. file 43
QCGEGLCCDQCSFIEEGTVCRIARGDDLDDYCNGRSAGCPRNP
QCGE---CDQCSFMKKGTICRRARGDDLDDYCNGRSAGCPRNP
QCGEGPCCDQCSFMKKGTICRRARGDDLDDYCNGRSAGCPRNP
QCGEGLCCDQCSFMKKGTICRRARGDDLDDYCNGISAGCPRNP
QCGEGLCCDQCSFMKKGTICRRARGDDLDDYCNGISAGCPRNP
QCADGLCCDQCRFKKKRTICRRARGDD--DRCTGQSADCPRNG
QCADGLCCDQCRFKKKTGICRIARGDFPDDRCTGLSNDCPRWN
Q--DGLCCDQCRFKKKRTICRIARGDFPDDRCTGQSADCPRWN
QCAEGLCCDQCRFKGAGKICRRARGDNPDDRCTGQSADCPRNR
QCAEGLCCDQCLFMKEGTVC-RARGDDVNDYCNGISAGCPRNP
PCATGPCCRRCKFKRAGKVCRVARGDWNNDYCTGKSCDCPRNP

3) File of protein activities (with extension *.act).  Format of this file
is just activity value of each protein per line.  In case if you do not
need to investigate structure-activity relations or don't have activity
data just type ordinal numbers 1, 2, 3, 4, 5, ....  Add one or more blank
lines at the end of the file.

For example:

 1.602
 1.699
 1.716
 1.748
 1.982
 2
 2.033
 2.124
 2.134
 2.188
 2.204
 2.326


In this menu item user can also select any subset of the proteins
for analysis (use <Enter> key to select or unselect particular protein).

There are several examples on the distribution disk.  They could be
useful to try the program and have a look at the structure of
data files.

4) File of residue solvent exposure and protein 2D structure (file name
with extension *.exp).  This file is optional.

Format of the file:
The file should have two lines of the length equal to the length of
aligned protein sequences.  First line characterizes the exposure of
amino acids (aa) to the solvent (0 - internal aa, 1 - external).
Positions containing 1 are marked green in the sequence window.  The
second string is simply displayed on the screen. So, you can type any
appropriate codes for the elements of the secondary structure.

Example:
1010110010011011001100011100101110101001100110100100000000000000000010
tttaaaaaaaaaaaaaaaaaattttttttttttbbbbbbbbbtttttttttaaaaaaaaaaaaaaaattt

There are several special command keys which facilitate the extraction of
any protein subset from the initial files.

  Command keys          Effect

   < Esc >              Return back.
   < Up Arrow >         Moves cursor one line up.
   < Down Arrow >       Moves cursor one line down.
   < Enter >            Selects/unselects the protein.
   < Alt I >            Selects all proteins.
   < Alt C >            Unselects all selected proteins.
   < PgUp >             Moves cursor seventeen lines up.
   < PgDn >             Moves cursor seventeen lines down.

   CAUTION:  The following limits are in the current version of the
program:
 -  the  length  of  aligned  sequences must be less than or equal to 5000
amino acid residues;
 - the length of protein name can not have more than 80 symbols;
 - the numbers of proteins should not exceed 500.
#213
LOAD 3D-STRUCTURE.
User can load 3D structure of one of the analyzed proteins. This
structure will be used as a model for all analyzed proteins.  The files
containing 3D data (.cb,.pdb) are supposed to be in PDB format.
PROANALYST is able to work with files containing only C-alpha, C-beta
atoms or all protein atoms. The part of 3D structure can be loaded too.
#214
- Result -

This options allows to see all results of PROANALYST calculation (files
with filenames having the extension *.res).  The whole library of results
can be created while working with the program.

   F3 key is used to see the files.
   F4 key is used to edit the files.
#215
- Save protein -

User can save to disk any subset of initially selected protein family and
activities in a form appropriate for further using (&Load Protein&212).
All sequences from groups with numbers 1, 2, 3, etc.  (except group with
number 0) will be saved.  After using of this option the window appear
that have file directory with extensions *.ALI.  In order to create new
file it is necessary to type the new filename and ENTER.  In order to
append existing file, chose the name and type ENTER.  You can enter to
the section "Save protein" only if the options &File&21,
&Load Protein&212 and &Prepare data&23 are executed.

&Main menu&2

#800
- Load protein from PDB file -

Load protein sequence from PDB file. This option is available only after
protein 3D-structure is made loaded (&Load 3D-struct&213).

#216
- Commander -

   In this option the user can execute any of DOS command.

&Main menu&2
#2211

User chooses the type of data to be used in calculation:
1. Only 1D-structure
2. Only 3D-structure
3. 1D-structure and 3D-structure

&Main menu&2

#2214@
HYPOTHESES AMOUNT

Maximal amount of protein fragments
(sites) to be displayed on the screen
as the result of automatic search.
User can select any number up to 200.
Default value is 25.

#2215@
- Min frame, Max frame -
    Minimal  and  Maximal
length  of  protein  fragments
to be searched for (for automatic search).
(Min > or = 1, Max < length
of the studied protein region).
Default values are: MIN FRAME=1, MAX FRAME=5.

#2218
GAPS TREATMENT

In this section user can to select a way how to proceed with gaps.
There are two ways of processing gaps: in mode "Ignore" gaps will be
omitted (for example, sequence ACDE--FG will turn into ACDEFG).  In
mode "Exclude" sequences having gaps will be excluded from
calculation of fragment characteristic.  The second way is based on
the point of view that deletions greatly distort local protein
structure and sites with the gaps can not be analyzed adequately by
such a simple procedure (and hence there is no reason to take into
account sites having gaps).  Default value is IGNORE.

&Main menu&2
#2219
- Fragments. -

There are two modes of working:

  SPLIT  - Each marked fragment is site for investigation.

  MERGE - Combine several marked fragments (with numbers 1, 2, 3,... etc.)
          to one discrete site.  Only average, sum,  min and max functions
          are appropriate in this case.  Default value is: SPLIT.


Default value is: SPLIT.
&Main menu&2
#22110
- Number evaluate factors. -

   Min and  max number of evaluated factors for regression and
discriminant analysis.

Default values are: 1 and 1.

&Main menu&2
#22112@
CUTOFF RADIUS

CUTOFF RADIUS is threshold distance
(between C-alpha, C-beta or all atoms)
for creation of spatial sites. Default
value is: 5 angstroms.

#22113@
TYPE OF INPUT ATOMS.

The type of atoms is show (CA or CB or
ALL) that will be used in analysis of
tertiary structures.  Choose what is
necessary in your case.  Default value
is: CA.

#22114
PROFILE SMOOTHING.

Switching On or Off the profile smoothing.  The value S(i) in
position i for unsmoothed profile is equal to protein site
characteristic calculated for the window [i,i+current frame].  The
formulae of smoothing is the following:

SS(i)= (S(i)+S(i-1)+S(i-2)+...+S(i-current frame))/current frame
Default value is: OFF.

&Main menu&2
#251
- SPATIAL SITE -

This module assign for viewing 3D-structure of proteins and spatial
sites. Protein sites marked in section &PREPARE DATA&23 (or
&VIEW LAST RESULT&249) will be shown here in colors.
The graphical module is highly flexible: there are three types of
residues in the protein, that may be treated separately:

A (SITE CENTERS) - sites, marked earlier in the PREPARE DATA menu item or
just now in this window (press ENTER on desired position) or as the
result of selecting site in submenu VIEW RESULTS;

B (NEIGHBORS) - the residues that are close to the SITE CENTERS (the cutoff
radius is given in menu items &CALCULATION&221);

C (PROTEIN) - all other residues of protein.

The style to display residues of types A,B,C can be changed independently
(see help- lines at the top and the bottom of the screen).  Amino acid
sequence of the protein is shown on the screen (the sequence is taken from
PDB-file but not from *.ali file). The colors of the letters related to the
colors of residues on the stereo picture.  This module can be used also
independently to display protein structures (without loading any protein
family for analysis).

User has options to:

- display alternatively C-alpha or all-atom protein models;

- rotate the structure, change the dimensions of the picture, stereo
angle, distance between stereo pictures (even to display mono
pictures);

-change the width of the main chain and the backbone, the colors of types
A, B and C residues (the site, its neighbors and the rest of the
molecule);

- change the size and colors of C-alpha atoms;

- create spatial site (by moving cursor through backbone and pressing
"ENTER");

- print picture to printer.

The following functional keys are used in the program (they are is  shown
on the bottom line of the screen):

-------------------------------------------------------------------------
F2-PROTEIN  F3-SITE CENTERS   F4-NEIGHBORS  F5-OPTIONS  F6-PRINT F10-QUIT
-------------------------------------------------------------------------

Command key     Effect

F2-PROTEIN      change the modes to display the residues of the type C.

F3-SITE CENTERS change the modes to display the residues that are
                CENTERS OF THE SITES marked earlier in PREPARE DATA or
                here (type A).

F3-NEIGHBORS    change the modes to display the residues that are
                within cutoff radius from CENTERS OF THE SITES (type B).

F5-OPTIONS      change the numeration, picture size, distance between the
                stereo pictures, stereo angle.

F6-PRINT        prints the picture to printer (laser or matrix).

F10-QUIT        return back.

After pressing F2, F3 or F4 the following submenu appears:

--------------------------------------------------------------------------
COLOR:SIDE CH,CA,BACKBONE,BACKGRND;WIDTH:SIDE CH,BACKBONE,CA;CHANGE:Grey+-
--------------------------------------------------------------------------

COLORS serves to change the colors of chosen types residues.  User can
change the colors of side chains (SIDE CH), C- alpha atoms (CA) and of
the protein backbone (BACKBONE).  The color of the screen background also
can be changed (BACKGRND).

WIDTH serves to change the width of chosen types residues.  User can
change the width of side chains (SIDE CH), of protein backbone (BACKBONE)
and of C-alpha atoms (CA).

To change any picture element it is necessary to move cursor to the
relative position (LEFT and RIGHT ARROW keys should be used) and press
key <GREY -> or <GREY +>.  Pressing <GREY -> or <GREY +> several times
you can get desirable size, color, numeration and width of the lines and
C-alpha atoms.  The width of the lines have three meanings: heavy lines,
thin lines and the absence of lines (last case helps you to remove some
parts of the structure from the picture if necessary).

In submenu item OPTIONS (F5) the following submenu appears:

-------------------------------------------------------------------------
NUMERATION SIZE DISTANCE-BETWEEN-PICT. STEREO-ANGLE;CHANGE:GREY<-,->,+,-
-------------------------------------------------------------------------

To change picture element it is necessary to move cursor to the relative
position (LEFT and RIGHT ARROW keys should be used) and press key <GREY ->
or <GREY +>.  Pressing <GREY -> or <GREY +> several times you can set
desirable options: change the numeration, picture size, distance between
the stereo pictures and stereo angle. (Increasing stereo angle to
90o, you'll get two pictures from the different sides of the protein).
#252
- SIMPLE MARKING -

This module serves for marking different amino acid residues groups
without relation to window with the sequences and without
automatic marking spatial neighbors (as in &SPATIAL SITE&251). All
amino acid residues are divided into three groups, that can be
treated separately: LOW GROUP, MEAN GROUP and HIGH GROUP. The
status of current group is displayed on the top left of the screen.
The style of displaying residues of these groups can be changed
independently.

The mode of working in this module is the same as in module SPATIAL SITE.

The help-line on the bottom of the screen is:

-------------------------------------------------------------------------
F2-MEAN GROUP F3-HIGH GROUP  F4-LOW GROUP  F5-OPTIONS  F6-PRINT  F10-QUIT
-------------------------------------------------------------------------

To change the current group options you should press relatively F2, F3 or
F4. The following submenu appears, that is the same as in
module SPATIAL SITE.

-------------------------------------------------------------------------
COLOR:SIDE CH,CA,BACKBONE,BACKGRND;WIDTH:SIDE CH,BACKBONE,CA;CHANGE:Grey+-
-------------------------------------------------------------------------

To change only the current group status (mean, high, low) you should press
F2 and <Esc>, F3 and <Esc>, F4 and <Esc>.

The colors of groups in 3D picture refer to the colors of letters in
the protein sequence on the bottom of the screen.

 &Main menu&2
#900

&PROANALYST&2 - QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIPS (QSAR) IN
PROTEINS, PROTEIN ENGINEERING, PATTERNS RECOGNITION IN COMBINATORIAL
LIBRARIES, PHYSICO-CHEMICAL AND ALPHABETICAL ANALYSIS FOR MULTIPLE
            SEQUENCE ALIGNMENTS AND 3D STRUCTURE

			   DEMO VERSION

     COPYRIGHT (C) 1996 Vladimir A.Ivanisenko, Alexey M.Eroshkin

  Theoretical Dept., Research Institute of Molecular Biology,
  SRC VB "Vector", 633159, Koltsovo, Novosibirsk region, Russia

  Tel. (3822) 647774
  Telex 133196 NPO SU
  Fax: (3832) 328831;
  E.mail: salex@vector.nsk.su, eroshkin@vector.nsk.su

PRESS ENTER TO CONTINUE
#901

&PROANALYST&23 - QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIPS (QSAR) IN
PROTEINS, PROTEIN ENGINEERING, PATTERNS RECOGNITION IN COMBINATORIAL
LIBRARIES, PHYSICO-CHEMICAL AND ALPHABETICAL ANALYSIS FOR MULTIPLE
            SEQUENCE ALIGNMENTS AND 3D STRUCTURE

			      DEMO VERSION
                             COPYRIGHT 1996
      Theoretical Dept., Research Institute of Molecular Biology,
     SRC VB 'Vector'. 633159, Koltsovo, Novosibirsk region, Russia
Tel.:  (3822) 647774
Telex: 133196 NPO SU
Fax:   (3832) 328831
E.mail: salex@vector.nsk.su, eroshkin@vector.nsk.su

Vladimir Ivanisenko
Alexey   Eroshkin                     PRESS ENTER TO CONTINUE
#902
- Key F1 -
The window for protein names editing.
  Command keys          Effect

   < Esc >              Return to work window of proteins.
   < Left >             Moves the cursor on one position to the left.
   < Right >            Moves the cursor on one position to the right.
   < Up >               Moves the string to up.
   < Down >             Moves the string to down.
   < Home >             Moves the cursor to the position of
                        first character on the name.
   < End >              Moves the cursor to the position of
                        end character on the name.
   < F4 >               Edit.
#903
- Key F1 -
The window for protein activities editing.
  Command keys          Effect

   < Esc >              Return to work window of proteins.
   < Up >               Moves the string to up.
   < Down >             Moves the string to down.
   < F4 >               Edit.
#904

&PROANALYST&21 - QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIPS (QSAR) IN
PROTEINS, PROTEIN ENGINEERING, PATTERNS RECOGNITION IN COMBINATORIAL
LIBRARIES, PHYSICO-CHEMICAL AND ALPHABETICAL ANALYSIS FOR MULTIPLE
            SEQUENCE ALIGNMENTS AND 3D STRUCTURE

			   DEMO VERSION

     COPYRIGHT (C) 1996 Vladimir A.Ivanisenko, Alexey M.Eroshkin

  Theoretical Dept., Research Institute of Molecular Biology,
  SRC VB "Vector", 633159, Koltsovo, Novosibirsk region, Russia

  Tel. (3822) 647774
  Telex 133196 NPO SU
  Fax: (3832) 328831;
  E.mail: salex@vector.nsk.su, eroshkin@vector.nsk.su

PRESS ENTER TO CONTINUE
#905

&PROANALYST&22 - QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIPS (QSAR) IN
PROTEINS, PROTEIN ENGINEERING, PATTERNS RECOGNITION IN COMBINATORIAL
LIBRARIES, PHYSICO-CHEMICAL AND ALPHABETICAL ANALYSIS FOR MULTIPLE
            SEQUENCE ALIGNMENTS AND 3D STRUCTURE

			   DEMO VERSION

     COPYRIGHT (C) 1996 Vladimir A.Ivanisenko, Alexey M.Eroshkin

  Theoretical Dept., Research Institute of Molecular Biology,
  SRC VB "Vector", 633159, Koltsovo, Novosibirsk region, Russia

  Tel. (3822) 647774
  Telex 133196 NPO SU
  Fax: (3832) 328831;
  E.mail: salex@vector.nsk.su, eroshkin@vector.nsk.su

PRESS ENTER TO CONTINUE
#906

&PROANALYST&221 - QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIPS (QSAR) IN
PROTEINS, PROTEIN ENGINEERING, PATTERNS RECOGNITION IN COMBINATORIAL
LIBRARIES, PHYSICO-CHEMICAL AND ALPHABETICAL ANALYSIS FOR MULTIPLE
            SEQUENCE ALIGNMENTS AND 3D STRUCTURE

			   DEMO VERSION

     COPYRIGHT (C) 1996 Vladimir A.Ivanisenko, Alexey M.Eroshkin

  Theoretical Dept., Research Institute of Molecular Biology,
  SRC VB "Vector", 633159, Koltsovo, Novosibirsk region, Russia

  Tel. (3822) 647774
  Telex 133196 NPO SU
  Fax: (3832) 328831;
  E.mail: salex@vector.nsk.su, eroshkin@vector.nsk.su

PRESS ENTER TO CONTINUE
#916

&PROANALYST&805 - QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIPS (QSAR) IN
PROTEINS, PROTEIN ENGINEERING, PATTERNS RECOGNITION IN COMBINATORIAL
LIBRARIES, PHYSICO-CHEMICAL AND ALPHABETICAL ANALYSIS FOR MULTIPLE
            SEQUENCE ALIGNMENTS AND 3D STRUCTURE

			   DEMO VERSION

     COPYRIGHT (C) 1996 Vladimir A.Ivanisenko, Alexey M.Eroshkin

  Theoretical Dept., Research Institute of Molecular Biology,
  SRC VB "Vector", 633159, Koltsovo, Novosibirsk region, Russia

  Tel. (3822) 647774
  Telex 133196 NPO SU
  Fax: (3832) 328831;
  E.mail: salex@vector.nsk.su, eroshkin@vector.nsk.su

PRESS ENTER TO CONTINUE
#907

&PROANALYST&2212 - QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIPS (QSAR) IN
PROTEINS, PROTEIN ENGINEERING, PATTERNS RECOGNITION IN COMBINATORIAL
LIBRARIES, PHYSICO-CHEMICAL AND ALPHABETICAL ANALYSIS FOR MULTIPLE
            SEQUENCE ALIGNMENTS AND 3D STRUCTURE

			   DEMO VERSION

     COPYRIGHT (C) 1996 Vladimir A.Ivanisenko, Alexey M.Eroshkin

  Theoretical Dept., Research Institute of Molecular Biology,
  SRC VB "Vector", 633159, Koltsovo, Novosibirsk region, Russia

  Tel. (3822) 647774
  Telex 133196 NPO SU
  Fax: (3832) 328831;
  E.mail: salex@vector.nsk.su, eroshkin@vector.nsk.su

PRESS ENTER TO CONTINUE
#908

&PROANALYST&2213 - QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIPS (QSAR) IN
PROTEINS, PROTEIN ENGINEERING, PATTERNS RECOGNITION IN COMBINATORIAL
LIBRARIES, PHYSICO-CHEMICAL AND ALPHABETICAL ANALYSIS FOR MULTIPLE
            SEQUENCE ALIGNMENTS AND 3D STRUCTURE

			   DEMO VERSION

     COPYRIGHT (C) 1996 Vladimir A.Ivanisenko, Alexey M.Eroshkin

  Theoretical Dept., Research Institute of Molecular Biology,
  SRC VB "Vector", 633159, Koltsovo, Novosibirsk region, Russia

  Tel. (3822) 647774
  Telex 133196 NPO SU
  Fax: (3832) 328831;
  E.mail: salex@vector.nsk.su, eroshkin@vector.nsk.su

PRESS ENTER TO CONTINUE
#909
- 909 -

&PROANALYST&2 - QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIPS (QSAR) IN
PROTEINS, PROTEIN ENGINEERING, PATTERNS RECOGNITION IN COMBINATORIAL
LIBRARIES, PHYSICO-CHEMICAL AND ALPHABETICAL ANALYSIS FOR MULTIPLE
            SEQUENCE ALIGNMENTS AND 3D STRUCTURE

			   DEMO VERSION

     COPYRIGHT (C) 1996 Vladimir A.Ivanisenko, Alexey M.Eroshkin

  Theoretical Dept., Research Institute of Molecular Biology,
  SRC VB "Vector", 633159, Koltsovo, Novosibirsk region, Russia

  Tel. (3822) 647774
  Telex 133196 NPO SU
  Fax: (3832) 328831;
  E.mail: salex@vector.nsk.su, eroshkin@vector.nsk.su

PRESS ENTER TO CONTINUE
#910

&PROANALYST&24 - QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIPS (QSAR) IN
PROTEINS, PROTEIN ENGINEERING, PATTERNS RECOGNITION IN COMBINATORIAL
LIBRARIES, PHYSICO-CHEMICAL AND ALPHABETICAL ANALYSIS FOR MULTIPLE
            SEQUENCE ALIGNMENTS AND 3D STRUCTURE

			   DEMO VERSION

     COPYRIGHT (C) 1996 Vladimir A.Ivanisenko, Alexey M.Eroshkin

  Theoretical Dept., Research Institute of Molecular Biology,
  SRC VB "Vector", 633159, Koltsovo, Novosibirsk region, Russia

  Tel. (3822) 647774
  Telex 133196 NPO SU
  Fax: (3832) 328831;
  E.mail: salex@vector.nsk.su, eroshkin@vector.nsk.su

PRESS ENTER TO CONTINUE
#911

&PROANALYST&2210 - QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIPS (QSAR) IN
PROTEINS, PROTEIN ENGINEERING, PATTERNS RECOGNITION IN COMBINATORIAL
LIBRARIES, PHYSICO-CHEMICAL AND ALPHABETICAL ANALYSIS FOR MULTIPLE
            SEQUENCE ALIGNMENTS AND 3D STRUCTURE

			   DEMO VERSION

     COPYRIGHT (C) 1996 Vladimir A.Ivanisenko, Alexey M.Eroshkin

  Theoretical Dept., Research Institute of Molecular Biology,
  SRC VB "Vector", 633159, Koltsovo, Novosibirsk region, Russia

  Tel. (3822) 647774
  Telex 133196 NPO SU
  Fax: (3832) 328831;
  E.mail: salex@vector.nsk.su, eroshkin@vector.nsk.su

PRESS ENTER TO CONTINUE
#915

&PROANALYST&242 - QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIPS (QSAR) IN
PROTEINS, PROTEIN ENGINEERING, PATTERNS RECOGNITION IN COMBINATORIAL
LIBRARIES, PHYSICO-CHEMICAL AND ALPHABETICAL ANALYSIS FOR MULTIPLE
            SEQUENCE ALIGNMENTS AND 3D STRUCTURE

			   DEMO VERSION

     COPYRIGHT (C) 1996 Vladimir A.Ivanisenko, Alexey M.Eroshkin

  Theoretical Dept., Research Institute of Molecular Biology,
  SRC VB "Vector", 633159, Koltsovo, Novosibirsk region, Russia

  Tel. (3822) 647774
  Telex 133196 NPO SU
  Fax: (3832) 328831;
  E.mail: salex@vector.nsk.su, eroshkin@vector.nsk.su

PRESS ENTER TO CONTINUE
#920

&PROANALYST&244 - QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIPS (QSAR) IN
PROTEINS, PROTEIN ENGINEERING, PATTERNS RECOGNITION IN COMBINATORIAL
LIBRARIES, PHYSICO-CHEMICAL AND ALPHABETICAL ANALYSIS FOR MULTIPLE
            SEQUENCE ALIGNMENTS AND 3D STRUCTURE

			   DEMO VERSION

     COPYRIGHT (C) 1996 Vladimir A.Ivanisenko, Alexey M.Eroshkin

  Theoretical Dept., Research Institute of Molecular Biology,
  SRC VB "Vector", 633159, Koltsovo, Novosibirsk region, Russia

  Tel. (3822) 647774
  Telex 133196 NPO SU
  Fax: (3832) 328831;
  E.mail: salex@vector.nsk.su, eroshkin@vector.nsk.su

PRESS ENTER TO CONTINUE
#925

&PROANALYST&249 - QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIPS (QSAR) IN
PROTEINS, PROTEIN ENGINEERING, PATTERNS RECOGNITION IN COMBINATORIAL
LIBRARIES, PHYSICO-CHEMICAL AND ALPHABETICAL ANALYSIS FOR MULTIPLE
            SEQUENCE ALIGNMENTS AND 3D STRUCTURE

			   DEMO VERSION

     COPYRIGHT (C) 1996 Vladimir A.Ivanisenko, Alexey M.Eroshkin

  Theoretical Dept., Research Institute of Molecular Biology,
  SRC VB "Vector", 633159, Koltsovo, Novosibirsk region, Russia

  Tel. (3822) 647774
  Telex 133196 NPO SU
  Fax: (3832) 328831;
  E.mail: salex@vector.nsk.su, eroshkin@vector.nsk.su

PRESS ENTER TO CONTINUE
#930

&PROANALYST&241 - QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIPS (QSAR) IN
PROTEINS, PROTEIN ENGINEERING, PATTERNS RECOGNITION IN COMBINATORIAL
LIBRARIES, PHYSICO-CHEMICAL AND ALPHABETICAL ANALYSIS FOR MULTIPLE
            SEQUENCE ALIGNMENTS AND 3D STRUCTURE

			   DEMO VERSION

     COPYRIGHT (C) 1996 Vladimir A.Ivanisenko, Alexey M.Eroshkin

  Theoretical Dept., Research Institute of Molecular Biology,
  SRC VB "Vector", 633159, Koltsovo, Novosibirsk region, Russia

  Tel. (3822) 647774
  Telex 133196 NPO SU
  Fax: (3832) 328831;
  E.mail: salex@vector.nsk.su, eroshkin@vector.nsk.su

PRESS ENTER TO CONTINUE
#935

&PROANALYST&241 - QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIPS (QSAR) IN
PROTEINS, PROTEIN ENGINEERING, PATTERNS RECOGNITION IN COMBINATORIAL
LIBRARIES, PHYSICO-CHEMICAL AND ALPHABETICAL ANALYSIS FOR MULTIPLE
            SEQUENCE ALIGNMENTS AND 3D STRUCTURE

			   DEMO VERSION

     COPYRIGHT (C) 1996 Vladimir A.Ivanisenko, Alexey M.Eroshkin

  Theoretical Dept., Research Institute of Molecular Biology,
  SRC VB "Vector", 633159, Koltsovo, Novosibirsk region, Russia

  Tel. (3822) 647774
  Telex 133196 NPO SU
  Fax: (3832) 328831;
  E.mail: salex@vector.nsk.su, eroshkin@vector.nsk.su

PRESS ENTER TO CONTINUE
#940

&PROANALYST&241 - QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIPS (QSAR) IN
PROTEINS, PROTEIN ENGINEERING, PATTERNS RECOGNITION IN COMBINATORIAL
LIBRARIES, PHYSICO-CHEMICAL AND ALPHABETICAL ANALYSIS FOR MULTIPLE
            SEQUENCE ALIGNMENTS AND 3D STRUCTURE

			   DEMO VERSION

     COPYRIGHT (C) 1996 Vladimir A.Ivanisenko, Alexey M.Eroshkin

  Theoretical Dept., Research Institute of Molecular Biology,
  SRC VB "Vector", 633159, Koltsovo, Novosibirsk region, Russia

  Tel. (3822) 647774
  Telex 133196 NPO SU
  Fax: (3832) 328831;
  E.mail: salex@vector.nsk.su, eroshkin@vector.nsk.su

PRESS ENTER TO CONTINUE
#945

&PROANALYST&2421 - QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIPS (QSAR) IN
PROTEINS, PROTEIN ENGINEERING, PATTERNS RECOGNITION IN COMBINATORIAL
LIBRARIES, PHYSICO-CHEMICAL AND ALPHABETICAL ANALYSIS FOR MULTIPLE
            SEQUENCE ALIGNMENTS AND 3D STRUCTURE

			   DEMO VERSION

     COPYRIGHT (C) 1996 Vladimir A.Ivanisenko, Alexey M.Eroshkin

  Theoretical Dept., Research Institute of Molecular Biology,
  SRC VB "Vector", 633159, Koltsovo, Novosibirsk region, Russia

  Tel. (3822) 647774
  Telex 133196 NPO SU
  Fax: (3832) 328831;
  E.mail: salex@vector.nsk.su, eroshkin@vector.nsk.su

PRESS ENTER TO CONTINUE
#950

&PROANALYST&2422 - QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIPS (QSAR) IN
PROTEINS, PROTEIN ENGINEERING, PATTERNS RECOGNITION IN COMBINATORIAL
LIBRARIES, PHYSICO-CHEMICAL AND ALPHABETICAL ANALYSIS FOR MULTIPLE
            SEQUENCE ALIGNMENTS AND 3D STRUCTURE

			   DEMO VERSION

     COPYRIGHT (C) 1996 Vladimir A.Ivanisenko, Alexey M.Eroshkin

  Theoretical Dept., Research Institute of Molecular Biology,
  SRC VB "Vector", 633159, Koltsovo, Novosibirsk region, Russia

  Tel. (3822) 647774
  Telex 133196 NPO SU
  Fax: (3832) 328831;
  E.mail: salex@vector.nsk.su, eroshkin@vector.nsk.su

PRESS ENTER TO CONTINUE
#955

&PROANALYST&2423 - QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIPS (QSAR) IN
PROTEINS, PROTEIN ENGINEERING, PATTERNS RECOGNITION IN COMBINATORIAL
LIBRARIES, PHYSICO-CHEMICAL AND ALPHABETICAL ANALYSIS FOR MULTIPLE
            SEQUENCE ALIGNMENTS AND 3D STRUCTURE

			   DEMO VERSION

     COPYRIGHT (C) 1996 Vladimir A.Ivanisenko, Alexey M.Eroshkin

  Theoretical Dept., Research Institute of Molecular Biology,
  SRC VB "Vector", 633159, Koltsovo, Novosibirsk region, Russia

  Tel. (3822) 647774
  Telex 133196 NPO SU
  Fax: (3832) 328831;
  E.mail: salex@vector.nsk.su, eroshkin@vector.nsk.su

PRESS ENTER TO CONTINUE

#960

&PROANALYST&2424 - QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIPS (QSAR) IN
PROTEINS, PROTEIN ENGINEERING, PATTERNS RECOGNITION IN COMBINATORIAL
LIBRARIES, PHYSICO-CHEMICAL AND ALPHABETICAL ANALYSIS FOR MULTIPLE
            SEQUENCE ALIGNMENTS AND 3D STRUCTURE

			   DEMO VERSION

     COPYRIGHT (C) 1996 Vladimir A.Ivanisenko, Alexey M.Eroshkin

  Theoretical Dept., Research Institute of Molecular Biology,
  SRC VB "Vector", 633159, Koltsovo, Novosibirsk region, Russia

  Tel. (3822) 647774
  Telex 133196 NPO SU
  Fax: (3832) 328831;
  E.mail: salex@vector.nsk.su, eroshkin@vector.nsk.su

PRESS ENTER TO CONTINUE
#965

&PROANALYST&2425 - QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIPS (QSAR) IN
PROTEINS, PROTEIN ENGINEERING, PATTERNS RECOGNITION IN COMBINATORIAL
LIBRARIES, PHYSICO-CHEMICAL AND ALPHABETICAL ANALYSIS FOR MULTIPLE
            SEQUENCE ALIGNMENTS AND 3D STRUCTURE

			   DEMO VERSION

     COPYRIGHT (C) 1996 Vladimir A.Ivanisenko, Alexey M.Eroshkin

  Theoretical Dept., Research Institute of Molecular Biology,
  SRC VB "Vector", 633159, Koltsovo, Novosibirsk region, Russia

  Tel. (3822) 647774
  Telex 133196 NPO SU
  Fax: (3832) 328831;
  E.mail: salex@vector.nsk.su, eroshkin@vector.nsk.su

PRESS ENTER TO CONTINUE

#970

&PROANALYST&2427 - QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIPS (QSAR) IN
PROTEINS, PROTEIN ENGINEERING, PATTERNS RECOGNITION IN COMBINATORIAL
LIBRARIES, PHYSICO-CHEMICAL AND ALPHABETICAL ANALYSIS FOR MULTIPLE
            SEQUENCE ALIGNMENTS AND 3D STRUCTURE

			   DEMO VERSION

     COPYRIGHT (C) 1996 Vladimir A.Ivanisenko, Alexey M.Eroshkin

  Theoretical Dept., Research Institute of Molecular Biology,
  SRC VB "Vector", 633159, Koltsovo, Novosibirsk region, Russia

  Tel. (3822) 647774
  Telex 133196 NPO SU
  Fax: (3832) 328831;
  E.mail: salex@vector.nsk.su, eroshkin@vector.nsk.su

PRESS ENTER TO CONTINUE
#980
- Key F1 -
980