title: Extending RosettaDock with water, sugar, and pH for prediction of complex structures and affinities for CAPRI rounds 20-27.
abstract: Rounds 20-27 of the Critical Assessment of PRotein Interactions (CAPRI) provided a testing platform for computational methods designed to address a wide range of challenges. The diverse targets drove the creation of and new combinations of computational tools. In this study, RosettaDock and other novel Rosetta protocols were used to successfully predict four of the 10 blind targets. For example, for DNase domain of Colicin E2-Im2 immunity protein, RosettaDock and RosettaLigand were used to predict the positions of water molecules at the interface, recovering 46% of the native water-mediated contacts. For α-repeat Rep4-Rep2 and g-type lysozyme-PliG inhibitor complexes, homology models were built and standard and pH-sensitive docking algorithms were used to generate structures with interface RMSD values of 3.3 Å and 2.0 Å, respectively. A novel flexible sugar-protein docking protocol was also developed and used for structure prediction of the BT4661-heparin-like saccharide complex, recovering 71% of the native contacts. Challenges remain in the generation of accurate homology models for protein mutants and sampling during global docking. On proteins designed to bind influenza hemagglutinin, only about half of the mutations were identified that affect binding (T55: 54%; T56: 48%). The prediction of the structure of the xylanase complex involving homology modeling and multidomain docking pushed the limits of global conformational sampling and did not result in any successful prediction. The diversity of problems at hand requires computational algorithms to be versatile; the recent additions to the Rosetta suite expand the capabilities to encompass more biologically realistic docking problems.
authors.affiliation: Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, Maryland.
authors.forename: Krishna Praneeth
authors.initials: KP
authors.lastname: Kilambi
authors.forename: Michael S
authors.initials: MS
authors.lastname: Pacella
authors.forename: Jianqing
authors.initials: J
authors.lastname: Xu
authors.forename: Jason W
authors.initials: JW
authors.lastname: Labonte
authors.forename: Justin R
authors.initials: JR
authors.lastname: Porter
authors.forename: Pravin
authors.initials: P
authors.lastname: Muthu
authors.forename: Kevin
authors.initials: K
authors.lastname: Drew
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kuroda
authors.forename: Ora
authors.initials: O
authors.lastname: Schueler-Furman
authors.forename: Richard
authors.initials: R
authors.lastname: Bonneau
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Gray
mesh_terms: D002241:Carbohydrates / Q000737:chemistry*; D003087:Colicins / Q000737:chemistry*; D019295:Computational Biology; D003851:Deoxyribonucleases / Q000737:chemistry; D006493:Heparin / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D062105:Molecular Docking Simulation; D046912:Multiprotein Complexes / Q000737:chemistry*; D009154:Mutation; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D012984:Software; D014867:Water / Q000737:chemistry*
chemical_list: D002241:Carbohydrates; D003087:Colicins; D046912:Multiprotein Complexes; D014867:Water; D006493:Heparin; D003851:Deoxyribonucleases
keywords: CAPRI; binding; protein docking; protein interactions