The relative helix and hydrogen bond stability in the B domain of protein A as revealed by integrated tempering sampling molecular dynamics simulation

doi:10.1063/1.3630127

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	The relative helix and hydrogen bond stability in the B domain of protein A as revealed by integrated tempering sampling molecular dynamics simulation
	Shao, Qiang; Gao, Yi Qin
刊名	JOURNAL OF CHEMICAL PHYSICS
	2011-10-07
卷号	135 期号:13
ISSN号	0021-9606
DOI	10.1063/1.3630127
英文摘要	Molecular dynamics simulations using the integrated tempering sampling method were performed for the folding of wild-type B domain of protein A (BdpA). Starting from random and stretched structures, these simulations allow us to fold this protein into the native-like structure frequently, achieving very small backbone (1.7 angstrom) and all heavy-atom root-mean-square deviation (2.6 angstrom). Therefore, the method used here increases the efficiency of configuration sampling and thermodynamics characterization by molecular dynamics simulation. Although inconsistency exists between the calculation and experiments for the absolute stabilities, as a limitation of the force field parameters, the calculated order of helix stability (H3 > H2 > H1) is consistent with that determined by experiments for individual separate helices. The lowest free energy folding pathway of BdpA was found to start with a barrierless and non-cooperative structural collapse from the entirely extended (E) state, which leads to a physiologically unfolded (P) state consisting of multiple stable structures with few native inter-helical hydrophobic interactions formed. In the P state, only H3 is fully structured. The final formation of H1 (and to a lesser extent, H2) in the folded (F) state requires the packing of the inter-helical hydrophobic contacts. In addition, it was found that stabilities of backbone hydrogen bonds are significantly affected by their positions relative to the inter-helical hydrophobic core. As temperature increases, the stability of the hydrogen bonds exposed to the solvent tends to increase while that of the hydrogen bonds buried within the hydrophobic core decreases. Finally, we discuss implications of this study on the general folding mechanism of proteins. (C) 2011 American Institute of Physics. [doi:10.1063/1.3630127]
语种	英语
出版者	AMER INST PHYSICS
WOS记录号	WOS:000295625400069
内容类型	期刊论文
源URL	[http://ir.iccas.ac.cn/handle/121111/73897]
专题	中国科学院化学研究所
通讯作者	Gao, Yi Qin
作者单位	Peking Univ, Beijing Natl Lab Mol Sci, Coll Chem & Mol Engn, Beijing 100871, Peoples R China
推荐引用方式 GB/T 7714	Shao, Qiang,Gao, Yi Qin. The relative helix and hydrogen bond stability in the B domain of protein A as revealed by integrated tempering sampling molecular dynamics simulation[J]. JOURNAL OF CHEMICAL PHYSICS,2011,135(13).
APA	Shao, Qiang,&Gao, Yi Qin.(2011).The relative helix and hydrogen bond stability in the B domain of protein A as revealed by integrated tempering sampling molecular dynamics simulation.JOURNAL OF CHEMICAL PHYSICS,135(13).
MLA	Shao, Qiang,et al."The relative helix and hydrogen bond stability in the B domain of protein A as revealed by integrated tempering sampling molecular dynamics simulation".JOURNAL OF CHEMICAL PHYSICS 135.13(2011).