Protein Flexibility in Ligand Docking

Principal Investigator:

Protein Flexibility in Ligand Docking

Proteins flex and change shape upon binding of a ligand. This flexible fit results in motions of the protein backbone and side-chains that maximise interactions with a high affinity ligand. This flexibility results in different cavity shapes, binding-site topology and of course severe problems in trying to dock different ligands, which are known to bind, into sites of the 'wrong' shape. To overcome this, in a time efficient manner, we have explored various methods of including protein and ligand flexibility into the docking process in order to solve this 'cross-docking' problem. This has included analytical and heuristic approaches to determine conformations of ligand and protein that are complimentary for tight binding. This is a very large compute problem, so the development of efficient algorithms is critical to the exploration of the available conformational spaces of the protein and ligand. Charaka Goonatilake is a PhD student in the Glen group developing new algorithms to explore solutions to this problem.

Summary

Date:

Jan 2005 - Dec 2009

Members:

Professor Robert C Glen

Partners & Collaborators:

Unilever