title: HingeMaster: normal mode hinge prediction approach and integration of complementary predictors.
abstract: Protein motion is often the link between structure and function and a substantial fraction of proteins move through a domain hinge bending mechanism. Predicting the location of the hinge from a single structure is thus a logical first step towards predicting motion. Here, we describe ways to predict the hinge location by grouping residues with correlated normal-mode motions. We benchmarked our normal-mode based predictor against a gold standard set of carefully annotated hinge locations taken from the Database of Macromolecular Motions. We then compared it with three existing structure-based hinge predictors (TLSMD, StoneHinge, and FlexOracle), plus HingeSeq, a sequence-based hinge predictor. Each of these methods predicts hinges using very different sources of information-normal modes, experimental thermal factors, bond constraint networks, energetics, and sequence, respectively. Thus it is logical that using these algorithms together would improve predictions. We integrated all the methods into a combined predictor using a weighted voting scheme. Finally, we encapsulated all our results in a web tool which can be used to run all the predictors on submitted proteins and visualize the results.
authors.affiliation: Department of Physics, Yale University, New Haven, Connecticut 06520, USA. samuel.flores@aya.yale.edu
authors.forename: Samuel C
authors.initials: SC
authors.lastname: Flores
authors.forename: Kevin S
authors.initials: KS
authors.lastname: Keating
authors.forename: Jay
authors.initials: J
authors.lastname: Painter
authors.forename: Faruck
authors.initials: F
authors.lastname: Morcos
authors.forename: Khang
authors.initials: K
authors.lastname: Nguyen
authors.forename: Ethan A
authors.initials: EA
authors.lastname: Merritt
authors.forename: Leslie A
authors.initials: LA
authors.lastname: Kuhn
authors.forename: Mark B
authors.initials: MB
authors.lastname: Gerstein
mesh_terms: D000465:Algorithms; D026921:Amino Acid Transport Systems, Neutral / Q000737:chemistry; D019295:Computational Biology / Q000379:methods; D003198:Computer Simulation; D030562:Databases, Protein; D029968:Escherichia coli Proteins / Q000737:chemistry; D006801:Humans; D007781:Lactoferrin / Q000737:chemistry; D008958:Models, Molecular; D009038:Motion; D017434:Protein Structure, Tertiary; D020539:Sequence Analysis, Protein / Q000379:methods*; D012984:Software
chemical_list: D026921:Amino Acid Transport Systems, Neutral; D029968:Escherichia coli Proteins; C528486:glnH protein, E coli; D007781:Lactoferrin