GSOC2010 Joao

Revision as of 01:23, 20 May 2010

Author & Mentors

João Rodrigues anaryin@gmail.com

Mentors

Eric Talevich

Diana Jaunzeikare

Peter Cock

Abstract

Biopython is a very popular library in Bioinformatics and Computational Biology. Its Bio.PDB module, originally developed by Thomas Hamelryck, is a simple yet powerful tool for structural biologists. Although it provides a reliable PDB parser feature and it allows several calculations (Neighbour Search, RMS) to be made on macromolecules, it still lacks a number of features that are part of a researcher's daily routine. Probing for disulphide bridges in a structure and adding polar hydrogen atoms accordingly are two examples that can be incorporated in Bio.PDB, given the module's clever structure and good overall organisation. Cosmetic operations such as chain removal and residue renaming – to account for the different existing nomenclatures – and renumbering would also be greatly appreciated by the community.

Another aspect that can be improved for Bio.PDB is a smooth integration/interaction layer for heavy-weights in macromolecule simulation such as MODELLER, GROMACS, AutoDock, HADDOCK. It could be argued that the easiest solution would be to code hooks to these packages' functions and routines. However, projects such as the recently developed edPDB or the more complete Biskit library render, in my opinion, such interfacing efforts redundant. Instead, I believe it to be more advantageous to include these software' input/output formats in Biopython's SeqIO and AlignIO modules. This, together with the creation of interfaces for model validation/structure checking services/software would allow Biopython to be used as a pre- and post-simulation tool. Eventually, it would pave the way for its inclusion in pipelines and workflows for structure modelling, molecular dynamics, and docking simulations.

Project Schedule

The schedule below was organised to be flexible, which means that some features will likely be done early. Also, the weeks include documentation and unit testing efforts for the features, with extended periods for reviewing these efforts at the two points during the project (halfway, final week).

Community Bonding Period

• Getting familiar with development environment (Git Hub account, Git, Biopython's repository, Bug tracking system, etc)

• Gather scientific literature and discuss some of the to-be-implemented methods.

Week 1 [31st May - 6th June]

Renumbering residues of a structure

• Read SEQRES record to account for gaps
• Alternatively read ATOM records.

Probe disulphide bridges in the structure

• Via NeighbourSearch class
• Also use SSBOND in header

Extract Biological Unit

• REMARK350 contains rotation and translation information
• If REMARK is absent, do nothing.

Week 2 [7th – 13th June]

Structure Hydrogenation

• Add all/polar hydrogens through interface with WHATIF server.
• Optionally define a set pH
  • pKa values algorithm

Hydrogenation Report

• Produces a brief list of polar hydrogen atoms in the structure.
  • Chain | Residue [number] | Atom

Weeks 3-5 [14th June- 4th July]

Removal of disordered atoms

• Solution proposed in the Biopython wiki

Residue name normalisation

• Build conversion table from different nomenclatures (research them during c.bonding period )
• Write function to make a given structure compliant with a given software nomenclature:
  • Amber
  • CNS/HADDOCK
  • GROMACS

Coarse Grain Structure

• Implement function to reduce complexity of a structure
  • 1pt*c-alpha
  • 2pt*c-alpha / c-beta
  • 3pt*c-alpha / c-beta / side-chain pseudo-centroid OR side-chain centroid

Week 6 (Mid-Term) [5th - 11th July]

Testing and consolidating the features thoroughly.

Write documentation & examples for each feature, to be included in Biopython's Wiki and Bio.PDB's FAQ.

Mid-term Evaluations. Discussing with mentors current state of project and adjust following schedule to comply with project's needs.

Week 7 [12th - 19th July]

Add support for MODELLER's PIR format to Biopython

• Format Description
• SeqIO
• AlignIO

Allow conversion of Structure Object to Sequence Object

• Based on Bio.PDB.Polypeptide function

Weeks 8-10 [20th July - 9th August]

Add Sequence/Structure Homology functions

• Create call to Biopython's BLAST interfaces
  • Allow direct blast from structure object ( e.g. protein.find_homoseq() )
  • Returns list of tuples with E-Value *Dictionary (name, length of alignment, etc..)
• Create interface with structural homology web services
  • e.g. Dali server
  • Return list of tuples with Z-Score*Dictionary (name, etc...)

Implement basic structure validation checks

• Via NeighbourSearch class
  • Same Charge contacts
  • Atom Clashes
• Via ResidueDepth Class
  • Buried Charges
• Interface WHATIF PDBReport web service
  • Parse WARNING and ERROR messages

Week 11 [10th - 17th August]

Reviewing documentation, code, write tests for new functions.