title: Protein-protein docking by fast generalized Fourier transforms on 5D rotational manifolds.
abstract: Energy evaluation using fast Fourier transforms (FFTs) enables sampling billions of putative complex structures and hence revolutionized rigid protein-protein docking. However, in current methods, efficient acceleration is achieved only in either the translational or the rotational subspace. Developing an efficient and accurate docking method that expands FFT-based sampling to five rotational coordinates is an extensively studied but still unsolved problem. The algorithm presented here retains the accuracy of earlier methods but yields at least 10-fold speedup. The improvement is due to two innovations. First, the search space is treated as the product manifold [Formula: see text], where [Formula: see text] is the rotation group representing the space of the rotating ligand, and [Formula: see text] is the space spanned by the two Euler angles that define the orientation of the vector from the center of the fixed receptor toward the center of the ligand. This representation enables the use of efficient FFT methods developed for [Formula: see text] Second, we select the centers of highly populated clusters of docked structures, rather than the lowest energy conformations, as predictions of the complex, and hence there is no need for very high accuracy in energy evaluation. Therefore, it is sufficient to use a limited number of spherical basis functions in the Fourier space, which increases the efficiency of sampling while retaining the accuracy of docking results. A major advantage of the method is that, in contrast to classical approaches, increasing the number of correlation function terms is computationally inexpensive, which enables using complex energy functions for scoring.
authors.affiliation: Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, NY 11794; Moscow Institute of Physics and Technology, Moscow Region 141700, Russia;
authors.forename: Dzmitry
authors.initials: D
authors.lastname: Padhorny
authors.affiliation: Moscow Institute of Physics and Technology, Moscow Region 141700, Russia;
authors.forename: Andrey
authors.initials: A
authors.lastname: Kazennov
authors.affiliation: Department of Biomedical Engineering, Boston University, Boston, MA 02215;
authors.forename: Brandon S
authors.initials: BS
authors.lastname: Zerbe
authors.affiliation: Department of Biomedical Engineering, Boston University, Boston, MA 02215;
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Porter
authors.affiliation: Department of Biomedical Engineering, Boston University, Boston, MA 02215;
authors.forename: Bing
authors.initials: B
authors.lastname: Xia
authors.affiliation: Department of Biomedical Engineering, Boston University, Boston, MA 02215;
authors.forename: Scott E
authors.initials: SE
authors.lastname: Mottarella
authors.affiliation: Moscow Institute of Physics and Technology, Moscow Region 141700, Russia; Innopolis University, Innopolis 420500, Russia; Institute of Computer Aided Design of the Russian Academy of Sciences, Moscow 123056, Russia;
authors.forename: Yaroslav
authors.initials: Y
authors.lastname: Kholodov
authors.affiliation: Inria Nancy, 54600 Villers-les-Nancy, France;
authors.forename: David W
authors.initials: DW
authors.lastname: Ritchie
authors.affiliation: Department of Biomedical Engineering, Boston University, Boston, MA 02215;
authors.forename: Sandor
authors.initials: S
authors.lastname: Vajda
authors.affiliation: Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, NY 11794; Laufer Center for Physical and Quantitative Biology, Stony Brook University, Stony Brook, NY 11794; Institute for Advanced Computational Sciences, Stony Brook University, Stony Brook, NY 11794 midas@laufercenter.org.
authors.forename: Dima
authors.initials: D
authors.lastname: Kozakov
mesh_terms: D000465:Algorithms; D005583:Fourier Analysis; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D062105:Molecular Docking Simulation / Q000379:methods*; D011485:Protein Binding; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D015203:Reproducibility of Results; D012399:Rotation; D013816:Thermodynamics
chemical_list: D011506:Proteins
keywords: FFT; manifold; protein docking