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PROANALYST: QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIPS IN
PROTEINS, PROTEIN ENGINEERING, PATTERNS RECOGNITION IN COMBINATORIAL
LIBRARIES, PHYSICO-CHEMICAL AND ALPHABETICAL ANALYSIS IN MULTIPLE
SEQUENCE ALIGNMENTS AND 3D STRUCTURE (VER 1.02)
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COPYRIGHT (C) 1996 Vladimir Ivanisenko, Alexey Eroshkin, all rights reserved.

State Research Center of Virology and Biotechnology "Vector" Koltsovo,
Novosibirsk Region, 633159 Russia
E.mail: salex@vector.nsk.su, eroshkin@vector.nsk.su

All Trademarks and Registered Names are acknowledged in this document.

The files required to run PROANALYST are distributed in the form of a
single compressed file. Create a directory "PANALYST" in your hard disk,
for example, C.  Copy PANALYS$ to the directory and type PANALYS$ to
unpack the program.

PROANALYST is an easy-to-use, state-of-the-art MSDOS application for
studying the relationships between structure and activity in
protein/peptide families.

You are free to use, copy and distribute this version to people you think
may have interest to it IF: NO FEE IS CHARGED FOR USE, COPYING OR
DISTRIBUTION. In this demo version print and save are disabled; the
number of analyzed proteins is limited by 15.

This program is provided without any warranty, expressed or implied to
you or any other person.  The authors will not be liable for incidental,
consequential or other damages arising through the use of this software.

You can copy the programs and give copies to other people.
However please note the following points: 
a. The copyright of the program remains with the authors.
b. Please acknowledge the program in any publications of
   research for which they are used.
c. If you transfer the program you must do so in unmodified form.

PROANALYST:

- has data converter from several protein sequence formats;
- finds sites (in multiple alignment and 3D structure) influencing
protein activity;
- finds relationships between protein site structural characteristics and
protein activities;
- investigates structural differences between proteins divided by
functional, evolutionary or other criteria (e.g. relates genotype to 
phenotype);
- investigates physico-chemical factors related with activity changes in
a set of mutant proteins (including multiple physico-chemical factors);
- simulates protein-engineering experiments and predicts activity of
mutant protein;
- searches motifs and patterns in combinatorial libraries 
(peptide and phage-displayed libraries);
- makes protein stereo pictures with sites highlighted;
- provides linear correlation analysis, multiple linear regression
analysis, discriminant analysis, ANOVA (analysis of variance),
alphabetical analysis, profile;
- maps all obtained results on 3D structure;
- makes multiple alignment visualization and editing.


       PROANALYST IS USEFUL:

     - for chemists and biochemists making the investigations in 
       the field of protein structure-function and structure-activity 
       analysis;

     - for protein engineers trying to improve some protein properties;

     - for molecular biologists that need to get sense from 
       multiple protein alignments; 

     - for those who are interested in protein evolution and  
       protein structure predictions; 

     - for those who need good color protein 3D pictures
       with marking different sites; 

     - for students in any field of PROTEIN SCIENCE that need to 
       know what is protein primary, secondary and tertiary 
       structures; hydrophilicity and flexibility of protein 
       segment; multiple alignments and sequences variability; 
       functional and activity-modulating sites; hydrophobic 
       moments; profiles of averages and variations; regression 
       and discriminant analysis and many other important things.  

     - for all persons who are interested in comparative protein 
       sequence analysis.

     PROANALYST has:

     - simple user interface to facilitate the data analysis and 
       design;
     - simple graphics to facilitate the data understanding;
     - data examples with some protein family sequences and structures;
     - data files of amino acid physico-chemical and other 
       properties commonly used in protein analysis;
     - the great number of service programs to help you in your
       research;
     - complete manual and help system.

REQUIREMENTS

PROANALYST runs on the IBM  PC  family  of  computers.  
PROANALYST requires DOS 3.30 or higher and at least 550K 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. 

THE PROGRAM'S MAIN FILES: 

README   TXT - this file
MANUAL   TXT - manual to PROANALYST    
HELP     HLP - help-file     
HELP1    EXE - program for on-line help
EXAMPLES TXT - step-by-step instruction to PROANALYST
PANALYST EXE - main program     
CONVERT  EXE - the program for data conversion from CLUSTAL, SWISS-PROT,
               PIR, GCG files to PROANALYST format
CONVERT  DOC - documentation for CONVERT
PROPERTY PPT - 19 useful phys.-chem. properties of amino acid residues    
KIDERA   PPT - 10 normalized Kidera's phys.-chem. properties of aa    
PROGRAPH PPT - phys.-chem. properties of aa (from PROFILEGRAPH, K.Hofmann)    
M2_RS    ACT - 3 files with data example of influenza A virus M(2) protein  
M2_RS    ALI     
M2_RS    SEQ     
ANTIMICR ACT - 3 files with data example of antimicrobial peptides   
ANTIMICR ALI     
ANTIMICR SEQ     
IFN      ACT - 3 files with data example of interferon-alpha  
IFN      SEQ  
IFN      ALI
IFN      EXP - amino acid exposure and secondary structure (optional)
IFN      PDB - interferon 3D structure 
DE1      ACT - 3 files with data example of disintegrins
DE1      SEQ
DE1      ALI
LIBRARY  ACT - 3 files with data example of phage-display library
LIBRARY  SEQ
LIBRARY  ALI
ALN (subdirectory) - 50 aligned protein families.


HOW TO START

To investigate the protein (or peptide) family of your interest you
should prepare 3 files with protein names (*.seq), protein activities or
grouping (*.act) and aligned sequences (*.ali) in the current directory.
The data preparation can be made with the using of program CONVERT (see
CONVERT.DOC) or any text editor.  See the formats in the MANUAL or in
the files with the examples. Simple editor and viewer are present also
in PROANALYST and CONVERT.

To use the program follow the steps: 

- start the program; 

- select earlier prepared protein family; 

- select sequences of the family you are going to investigate; 

- select a file with required physico-chemical properties of amino acids 
  (necessary for regression and discriminant analysis);
 
- select amino acid physico-chemical properties being interested; 

- select protein 3D structure (if available); 

- go to menu item PREPARE DATA; 

- define an investigated fragment (or up to 8 fragments); 

and so on.

All other information you'll get from MANUAL.TXT or EXAMPLES.TXT files or
from HELP system (press key F1) or simply with the using of trial-error
method.

If  you  have  problems  running PROANALYST please consult the manual 
or examples carefully to see if they can help.  If you still need
advice then please contact the authors by e-mail.

Ask authors for complete updated version and:

ADDITIONAL NEW SOFTWARE TOOLS:

ProMSED: Protein Multiple Sequence Editor (for MS Windows 3.x/95)

o automatic (Clustal V algorithm) and manual multiple protein sequences
alignment;
o sequences import and export in different formats;
o no limits on number and length of sequences except those imposed by
current computer memory;
o interactive alignment of selected protein subset or selected regions;
o flexible visualization and edition of alignment (Word for Windows
style);
o amino acid coloring to facilitate understanding protein
physico-chemical, structural, evolutionary and other features.


ProAnWin: Windows version of ProAnalyst with multiple protein
sequence alignment (for MS Windows 3.x/95)

o data input from main protein sequence formats (SWISS-PROT, PIR, FASTA,
GCG, CLUSTAL);
o databases of more then 50 amino acid physico-chemical properties;
o reads 3D protein structure in PDB format;
o flexible input of user-defined protein activities, properties or
related phenotypes;
o multiple protein sequences alignment (Clustal V algorithm);
o threading multiple sequence alignment onto known 3-dimensional
structure;
o searching sites influencing protein activity and analyzing
relationships between protein site structural characteristics and protein
activities (properties or related phenotypes);
o multiple linear regression analysis of structure-activity
relationships;
o genotype -- phenotype correlation analysis (e.g., in studying virus
drug resistance);
o investigation of physico-chemical factors related with activity or
property changes in mutant proteins;
o flexible visualization of protein 3D structures with sites highlighted;
o activity, property or phenotype prediction;
o output of all obtained results into text file.


PROANAL3: Protein structure-activity analysis, analysis of
physico-chemical properties variations and conservations (for MS DOS)

o main features of ProAnalyst with nonlinear analysis of protein
structure-activity relationships;
o enhanced physico-chemical profiles for protein features prediction
(functional and variable sites, secondary structures, amphipathic
helices, antigenic sites, etc.).