期刊
JOURNAL OF MOLECULAR BIOLOGY
卷 392, 期 3, 页码 823-836出版社
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jmb.2009.06.065
关键词
nitrogen regulatory protein C; quasi-harmonic analysis; conformational transition; simulation; targeted molecular dynamics
资金
- NIH [GM062117]
- DOE [DE-FG02-05ER15699]
- Howard Hughes Medical Institute
- U.S. Department of Energy (DOE) [DE-FG02-05ER15699] Funding Source: U.S. Department of Energy (DOE)
Recent advances in experimental methods provide increasing evidence that proteins sample the conformational substates that are important for function in the absence of their ligands. An example is the receiver domain of nitrogen regulatory protein C, a member of the phosphorylation-mediated signaling family of two-component systems. The receiver domain of nitrogen regulatory protein C samples both inactive conformation and the active conformation before phosphorylation. Here we determine a possible pathway of interconversion between the active state and the inactive state by targeted molecular dynamics simulations and quasi-harmonic analysis; these methods are used because the experimental conversion rate is in the high microsecond range, longer than those that are easily accessible to atomistic molecular dynamics simulations. The calculated pathway is found to be composed of four consecutive stages described by different progress variables. The lowest quasi-harmonic principal components from unbiased molecular dynamics simulations on the active state correspond to the first stage, but not to the subsequent stages of the transition. The targeted molecular dynamics pathway suggests that several transient nonnative hydrogen bonds may facilitate the transition. (C) 2009 Elsevier Ltd. All rights reserved.
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