title: A Markov-chain model description of binding funnels to enhance the ranking of docked solutions.
abstract: Within the crowded, seemingly chaotic environment of the cell, proteins are still able to find their binding partners. This is achieved via an ensemble of trajectories, which funnel them towards their functional binding sites, the binding funnel. Here, we characterize funnel-like energy structures on the global energy landscape using time-homogeneous finite state Markov chain models. These models are based on the idea that transitions can occur between structurally similar docking solutions, with transition probabilities determined by their difference in binding energy. Funnel-like energy structures are those containing solutions with very high equilibrium populations. Although these are found surrounding both near-native and false positive binding sites, we show that the removal of nonfunnel-like energy structures, by filtering away solutions with low maximum equilibrium population, can significantly improve the ranking of docked poses.
authors.affiliation: Biomolecular Modelling Laboratory, Cancer Research UK London Research Institute, London, WC2A 3LY, United Kingdom.
authors.forename: Mieczyslaw
authors.initials: M
authors.lastname: Torchala
authors.forename: Iain H
authors.initials: IH
authors.lastname: Moal
authors.forename: Raphael A G
authors.initials: RA
authors.lastname: Chaleil
authors.forename: Rudi
authors.initials: R
authors.lastname: Agius
authors.forename: Paul A
authors.initials: PA
authors.lastname: Bates
mesh_terms: D001665:Binding Sites; D003198:Computer Simulation; D008390:Markov Chains; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D011485:Protein Binding; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry*; D012984:Software; D012996:Solutions / Q000737:chemistry; D013816:Thermodynamics
chemical_list: D011506:Proteins; D012996:Solutions
keywords: Markovian dynamics; SwarmDock; node occupancies; protein conformational states; protein-protein docking funnels; scoring protein complexes