title: General order parameter based correlation analysis of protein backbone motions between experimental NMR relaxation measurements and molecular dynamics simulations.
abstract: Internal backbone dynamic motions are essential for different protein functions and occur on a wide range of time scales, from femtoseconds to seconds. Molecular dynamic (MD) simulations and nuclear magnetic resonance (NMR) spin relaxation measurements are valuable tools to gain access to fast (nanosecond) internal motions. However, there exist few reports on correlation analysis between MD and NMR relaxation data. Here, backbone relaxation measurements of (15)N-labeled SH3 (Src homology 3) domain proteins in aqueous buffer were used to generate general order parameters (S(2)) using a model-free approach. Simultaneously, 80 ns MD simulations of SH3 domain proteins in a defined hydrated box at neutral pH were conducted and the general order parameters (S(2)) were derived from the MD trajectory. Correlation analysis using the Gromos force field indicated that S(2) values from NMR relaxation measurements and MD simulations were significantly different. MD simulations were performed on models with different charge states for three histidine residues, and with different water models, which were SPC (simple point charge) water model and SPC/E (extended simple point charge) water model. S(2) parameters from MD simulations with charges for all three histidines and with the SPC/E water model correlated well with S(2) calculated from the experimental NMR relaxation measurements, in a site-specific manner.
authors.affiliation: Hefei National Laboratory for Physical Sciences at The Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, 230026, PR China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Hefei National Laboratory for Physical Sciences at The Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, 230026, PR China.
authors.forename: Chaowei
authors.initials: C
authors.lastname: Shi
authors.affiliation: Hefei National Laboratory for Physical Sciences at The Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, 230026, PR China; High Magnetic Field Laboratory, Chinese Academy of Science, Hefei, Anhui, 230031, PR China.
authors.forename: Lu
authors.initials: L
authors.lastname: Yu
authors.affiliation: Hefei National Laboratory for Physical Sciences at The Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, 230026, PR China.
authors.forename: Longhua
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Hefei National Laboratory for Physical Sciences at The Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, 230026, PR China. Electronic address: yxiong73@ustc.edu.cn.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xiong
authors.affiliation: Hefei National Laboratory for Physical Sciences at The Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, 230026, PR China; High Magnetic Field Laboratory, Chinese Academy of Science, Hefei, Anhui, 230031, PR China. Electronic address: cltian@ustc.edu.cn.
authors.forename: Changlin
authors.initials: C
authors.lastname: Tian
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry; D055592:Biophysical Phenomena; D006639:Histidine / Q000737:chemistry; D006801:Humans; D006859:Hydrogen / Q000737:chemistry; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D009038:Motion; D009124:Muscle Proteins; D009587:Nitrogen Isotopes; D019906:Nuclear Magnetic Resonance, Biomolecular; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry*; D014867:Water / Q000737:chemistry; D018909:src Homology Domains
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D009124:Muscle Proteins; D009587:Nitrogen Isotopes; D011506:Proteins; C486523:SORBS3 protein, human; D014867:Water; D006639:Histidine; D006859:Hydrogen
keywords: Charge states; General order parameters; Internal motion; Model-free approach; Molecular dynamic simulation; NMR relaxation