Andras Fiser
and 1 contributors

NAME

SmotifCS Hybrid Modeling Method

SYNOPSIS

Please read this document completely for running the SmotifCS software successfully on any local computer.

Pre-requisites:

The hybrid modeling algorithm requires a BMRB formatted chemical shift file as input. Additionally, if the structure of the protein is known from any alternate resource, then a PDB-formatted structure file is required. This pdb-file can be present in a centralized local directory or a user-designated separate directory.

Software / data:

1. MySQL - To install the Smotif Database

2. NMRPipe/TALOS - (http://spin.niddk.nih.gov/NMRPipe/)

3. Modeller (version 9.14 https://salilab.org/modeller/)

4. Phylip (version 3.69 http://evolution.genetics.washington.edu/phylip.html)

5. Local PDB directory (central or user-designated) - updated (http://www.rcsb.org).

Download and install the above mentioned software / data according to their instructions.

SmotifCS Download and Installation:

The following three components need to be downloaded and installed to run SmotifCS:

1. The software from CPAN (http://)

2. The Smotif library (http://fiserlab.org)

3. The chemical shift library (http://fiserlab.org)

Installation of the software (also available in the README file):

        tar -zxvf SmotifCS-0.01.tar.gz

        cd SmotifCS-0.01/

        perl Makefile.PL PREFIX=/home/user/SmotifCS-0.01

        make

        make test

        make install

Installation of the Smotif library using MYSQL:

Installation of the chemical shift library (flat files):

Set up the configuration file:

The configuration file, smotifcs_config.ini has all the information regarding the required library files and other pre-requisite software.

Set all the paths and executables in this file correctly.

Set environment varible in .bashrc file:

export SMOTIFCS_CONFIG_FILE=/home/user/SmotifCS-0.01/smotifcs_config.ini

        Modeling algorithm steps: 

         ----------------------------------------------------
        |Step 1:                                             |
        |       Run Talos+                                   |
        |       Get SS, Phi/PSi, Smotif Information          |
        |       Single-core job                              |
        |       Usage: perl smotifcs.pl --step=1 --pdb=1zzz  |
        |              --chain=A --havestructure=0           |
         ----------------------------------------------------

         ----------------------------------------------------
        |Step 2:                                             |
        |       Compare experimental CS of Query SmotifS     |       
        |       to theoretical CS of library Smotifs         |
        |       Multi-core / cluster job                     |
        |       Usage: perl smotifcs.pl --step=2 --pdb=1zzz  |
        |              --chain=A --havestructure=0           |
         ----------------------------------------------------

         ----------------------------------------------------
        |Step 3:                                             |
        |       Cluster and rank chosen SmotifS              |
        |                                                    |
        |       Multi-core / cluster job                     |  
        |       Usage: perl smotifcs.pl --step=3 --pdb=1zzz  |
        |              --chain=A --havestructure=0           |
         ----------------------------------------------------

         ----------------------------------------------------
        |Step 4:                                             |
        |       Enumerate all possible combinations of       |
        |       Smotifs (about a million models)             |
        |       Multi-core / cluster job                     |  
        |       Usage: perl smotifcs.pl --step=4 --pdb=1zzz  |
        |              --chain=A --havestructure=0           |
         ----------------------------------------------------

         ----------------------------------------------------
        |Step 5:                                             |
        |       Rank enumerated structures using a           |
        |       composite energy function                    |
        |       Single-core job                              |  
        |       Usage: perl smotifcs.pl --step=5 --pdb=1zzz  |
        |              --chain=A --havestructure=0           |
         ----------------------------------------------------

         ----------------------------------------------------
        |Step 6:                                             |
        |       Run Modeller to generate top 5 complete      |
        |       models                                       |
        |       Single-core job                              |  
        |       Usage: perl smotifcs.pl --step=6 --pdb=1zzz  |
        |              --chain=A --havestructure=0           |
         ----------------------------------------------------

How to run the program:

1. Create a subdirectory with a dummy pdb file name (eg: 1abc or 1zzz).

2. Put the chemical shift input file (in BMRB format) in this directory. Use the filename 1abc/pdb1abcshifts.dat or 1zzz/pdb1zzzshifts.dat for the BMRB formatted chemical shift input file.

3. Optional: If structure is known, include a pdb format structure file in the same directory. 1abc/pdb1abc.ent or 1zzz/pdb1zzz.ent

4. Run steps 1 to 6 as given above sequentially. Output from previous steps are often required in subsequent steps. Wait for each step to be completed without errors before going to the next step.

5. To run all steps together use: perl smotifcs.pl --step=all --pdb=1zzz --chain=A --havestructure=0

6. Use multiple-cores or clusters as available, for steps 2, 3 & 4. These are slow and require a lot of computational resources.

7. If structure is known, use --havestructure=1. Else, use --havestructure=0 in all the steps.

Results:

Top 5 models are stored in the subdirectory (1abc or 1zzz) as: Model.1.pdb, Model.2.pdb, Model.3.pdb, Model.4.pdb & Model.5.pdb

Reference:

Menon V, Vallat BK, Dybas JM, Fiser A. Modeling proteins using a super-secondary structure library and NMR chemical shift information. Structure, 2013, 21(6):891-9.

Authors:

Vilas Menon, Brinda Vallat, Joe Dybas, Carlos Madrid and Andras Fiser.

OPTIONS

-help

Print a brief help message and exits.

-man

Prints the manual page and exits.

--step

1,2,3,4,5,6 or all

--pdb

Give 4-letter dummy pdb_code

--chain

Give 1-letter chain_id

--havestructure

0 or 1 depending on whether a structure is known for the protein from alternate sources.

DESCRIPTION

SmotifCS will use the experimentally determined chemical shift information for a protein to model its complete structure using the Smotif library.