Designing coarse grained-and atom based-potentials for protein-protein docking

✍ Scribed by Dror Tobi

• Book ID: 104497920
• Publisher: BioMed Central
• Year: 2010
• Tongue: English
• Weight: 918 KB
• Volume: 10
• Category: Article
• ISSN: 1472-6807
• DOI: 10.1186/1472-6807-10-40

✦ Synopsis

Background:

Protein-protein docking is a challenging computational problem in functional genomics, particularly when one or both proteins undergo conformational change(s) upon binding. the major challenge is to define a scoring function soft enough to tolerate these changes and specific enough to distinguish between near-native and "misdocked" conformations.

Results:

Using a linear programming (lp) technique, we developed two types of potentials: (i) side chain-based and (ii) heavy atom-based. to achieve this we considered a set of 161 transient complexes and generated a large set of putative docked structures (decoys), based on a shape complementarity criterion, for each complex. the demand on the potentials was to yield, for the native (correctly docked) structure, a potential energy lower than those of any of the non-native (misdocked) structures. we show that the heavy atom-based potentials were able to comply with this requirement but not the side chain-based one. thus, despite the smaller number of parameters, the capability of heavy atom-based potentials to discriminate between native and "misdocked" conformations is improved relative to those of the side chain-based potentials. the performance of the atom-based potentials was evaluated by a jackknife test on a set of 50 complexes taken from the zdock2.3 decoys set.

Conclusions:

Our results show that, using the lp approach, we were able to train our potentials using a dataset of transient complexes only the newly developed potentials outperform three other known potentials in this test.