title: The impact of side-chain packing on protein docking refinement.
abstract: We study the impact of optimizing the side-chain positions in the interface region between two proteins during the process of binding. Mathematically, the problem is similar to side-chain prediction, which has been extensively explored in the process of protein structure prediction. The protein-protein docking application, however, has a number of characteristics that necessitate different algorithmic and implementation choices. In this work, we implement a distributed approximate algorithm that can be implemented on multiprocessor architectures and enables a trade-off between accuracy and running speed. We report computational results on benchmarks of enzyme-inhibitor and other types of complexes, establishing that the side-chain flexibility our algorithm introduces substantially improves the performance of docking protocols. Furthermore, we establish that the inclusion of unbound side-chain conformers in the side-chain positioning problem is critical in these performance improvements. The code is available to the community under open source license.
authors.affiliation: †Division of Systems Engineering, ‡Center for Information and Systems Engineering, §Department of Biomedical Engineering, ∥Department of Mechanical Engineering, and ⊥Department of Electrical and Computer Engineering, Boston University, Boston, Massachusetts 02215, United States.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Moghadasi
authors.affiliation: †Division of Systems Engineering, ‡Center for Information and Systems Engineering, §Department of Biomedical Engineering, ∥Department of Mechanical Engineering, and ⊥Department of Electrical and Computer Engineering, Boston University, Boston, Massachusetts 02215, United States.
authors.forename: Hanieh
authors.initials: H
authors.lastname: Mirzaei
authors.affiliation: †Division of Systems Engineering, ‡Center for Information and Systems Engineering, §Department of Biomedical Engineering, ∥Department of Mechanical Engineering, and ⊥Department of Electrical and Computer Engineering, Boston University, Boston, Massachusetts 02215, United States.
authors.forename: Artem
authors.initials: A
authors.lastname: Mamonov
authors.affiliation: †Division of Systems Engineering, ‡Center for Information and Systems Engineering, §Department of Biomedical Engineering, ∥Department of Mechanical Engineering, and ⊥Department of Electrical and Computer Engineering, Boston University, Boston, Massachusetts 02215, United States.
authors.forename: Pirooz
authors.initials: P
authors.lastname: Vakili
authors.affiliation: †Division of Systems Engineering, ‡Center for Information and Systems Engineering, §Department of Biomedical Engineering, ∥Department of Mechanical Engineering, and ⊥Department of Electrical and Computer Engineering, Boston University, Boston, Massachusetts 02215, United States.
authors.forename: Sandor
authors.initials: S
authors.lastname: Vajda
authors.affiliation: †Division of Systems Engineering, ‡Center for Information and Systems Engineering, §Department of Biomedical Engineering, ∥Department of Mechanical Engineering, and ⊥Department of Electrical and Computer Engineering, Boston University, Boston, Massachusetts 02215, United States.
authors.forename: Ioannis Ch
authors.initials: ICh
authors.lastname: Paschalidis
authors.affiliation: †Division of Systems Engineering, ‡Center for Information and Systems Engineering, §Department of Biomedical Engineering, ∥Department of Mechanical Engineering, and ⊥Department of Electrical and Computer Engineering, Boston University, Boston, Massachusetts 02215, United States.
authors.forename: Dima
authors.initials: D
authors.lastname: Kozakov
mesh_terms: D000465:Algorithms; D062105:Molecular Docking Simulation; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*; D013816:Thermodynamics; D013997:Time Factors
chemical_list: D011506:Proteins