Scoring a diverse set of high-quality docked conformations: a metascore based on electrostatic and desolvation interactions

Proteins
Carlos J CamachoP Christoph Champ

Abstract

Predicting protein-protein interactions involves sampling and scoring docked conformations. Barring some large structural rearrangement, rapidly sampling the space of docked conformations is now a real possibility, and the limiting step for the successful prediction of protein interactions is the scoring function used to reduce the space of conformations from billions to a few, and eventually one high affinity complex. An atomic level free-energy scoring function that estimates in units of kcal/mol both electrostatic and desolvation interactions (plus van der Waals if appropriate) of protein-protein docked conformations is used to rerank the blind predictions (860 in total) submitted for six targets to the community-wide Critical Assessment of PRediction of Interactions (CAPRI; http://capri.ebi.ac.uk). We found that native-like models often have varying intermolecular contacts and atom clashes, making unlikely that one can construct a universal function that would rank all these models as native-like. Nevertheless, our scoring function is able to consistently identify the native-like complexes as those with the lowest free energy for the individual models of 16 (out of 17) human predictors for five of the targets, while at the ...Continue Reading

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Sep 15, 2011·Journal of Computer-aided Molecular Design·Laurence Leherte, Daniel P Vercauteren
Jan 4, 2008·The Journal of Physical Chemistry. B·David L MobleyJohn D Chodera
Jun 1, 2007·Nucleic Acids Research·P Christoph Champ, Carlos J Camacho
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Jun 27, 2012·Journal of Molecular Recognition : JMR·Brian R WhiteCarston R Wagner
May 23, 2009·Journal of Computational Chemistry·Irina S MoreiraMaria J Ramos

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