Simultaneous Optimization of Biomolecular Energy Functions on Features   from Small Molecules and Macromolecules

doi:10.1021/acs.jctc.6b00819

CORC > 北京大学 > 生命科学学院

	Simultaneous Optimization of Biomolecular Energy Functions on Features from Small Molecules and Macromolecules
	Park, Hahnbeom ; Bradley, Philip ; Greisen, Per, Jr. ; Liu, Yuan ; Mulligan, Vikram Khipple ; Kim, David E. ; Baker, David ; DiMaio, Frank
刊名	JOURNAL OF CHEMICAL THEORY AND COMPUTATION
	2016
关键词	FORCE-FIELD SIDE-CHAIN DYNAMICS SIMULATIONS PROTEIN SIMULATIONS POTENTIAL FUNCTIONS LIQUID WATER PREDICTION MODEL SOLVENT SPECIFICITY
DOI	10.1021/acs.jctc.6b00819
英文摘要	Most biomolecular modeling energy functions for structure prediction, sequence design, and molecular docking have been parametrized using existing macromolecular structural data; this contrasts molecular mechanics force fields which are largely optimized using small-molecule data. In this study, we describe an integrated method that enables optimization of a biomolecular modeling energy function simultaneously against small-molecule thermodynamic data and high-resolution macromolecular structural data. We use this approach to develop a next-generation Rosetta energy function that utilizes a new anisotropic implicit solvation model, and an improved electrostatics and Lennard-Jones model, illustrating how energy functions can be considerably improved in their ability to describe large-scale energy landscapes by incorporating both small-molecule and macromolecule data. The energy function improves performance in a wide range of protein structure prediction challenges, including monomeric structure prediction, protein protein and protein ligand docking, protein sequence design, and prediction of the free energy changes by mutation, while reasonably recapitulating small-molecule thermodynamic properties.; US National Institutes of Health [R01GM092802]; SCI(E); ARTICLE; dimaio@u.washington.edu; 12; 6201-6212; 12
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/458273]
专题	生命科学学院
推荐引用方式 GB/T 7714	Park, Hahnbeom,Bradley, Philip,Greisen, Per, Jr.,et al. Simultaneous Optimization of Biomolecular Energy Functions on Features from Small Molecules and Macromolecules[J]. JOURNAL OF CHEMICAL THEORY AND COMPUTATION,2016.
APA	Park, Hahnbeom.,Bradley, Philip.,Greisen, Per, Jr..,Liu, Yuan.,Mulligan, Vikram Khipple.,...&DiMaio, Frank.(2016).Simultaneous Optimization of Biomolecular Energy Functions on Features from Small Molecules and Macromolecules.JOURNAL OF CHEMICAL THEORY AND COMPUTATION.
MLA	Park, Hahnbeom,et al."Simultaneous Optimization of Biomolecular Energy Functions on Features from Small Molecules and Macromolecules".JOURNAL OF CHEMICAL THEORY AND COMPUTATION (2016).