Mechanochemical Coupling in the Myosin Motor Domain. II. Analysis of Critical Residues

@article{citeulike:2434745, abstract = {An important challenge in the analysis of mechanochemical coupling in molecular motors is to identify residues that dictate the tight coupling between the chemical site and distant structural rearrangements. In this work, a systematic attempt is made to tackle this issue for the conventional myosin. By judiciously combining a range of computational techniques with different approximations and strength, which include targeted molecular dynamics, normal mode analysis, and statistical coupling analysis, we are able to identify a set of important residues and propose their relevant function during the recovery stroke of myosin. These analyses also allowed us to make connections with previous experimental and computational studies in a critical manner. The behavior of the widely used reporter residue, Trp501, in the simulations confirms the concern that its fluorescence does not simply reflect the relay loop conformation or active-site open/close but depends subtly on its microenvironment. The findings in the targeted molecular dynamics and a previous minimum energy path analysis of the recovery stroke have been compared and analyzed, which emphasized the difference and complementarity of the two approaches. In conjunction with our previous studies, the current set of investigations suggest that the modulation of structural flexibility at both the local (e.g., active-site) and domain scales with strategically placed \&\#8220;hotspot\&\#8221; residues and phosphate chemistry is likely the general feature for mechanochemical coupling in many molecular motors. The fundamental strategies of examining both collective and local changes and combining physically motivated methods and informatics-driven techniques are expected to be valuable to the study of other molecular motors and allosteric systems in general.}, author = {Yu, Haibo and Ma, Liang and Yang, Yang and Cui, Qiang }, citeulike-article-id = {2434745}, doi = {http://dx.doi.org/10.1371/journal.pcbi.0030023}, journal = {PLoS Computational Biology}, keywords = {analysis, md, motor, myosin, normal-mode}, month = {February}, number = {2}, pages = {e23+}, posted-at = {2008-02-27 07:15:45}, priority = {2}, title = {Mechanochemical Coupling in the Myosin Motor Domain. II. Analysis of Critical Residues}, url = {http://dx.doi.org/10.1371/journal.pcbi.0030023}, volume = {3}, year = {2007} }

TY - JOUR ID - citeulike:2434745 L3 - citeulike-article-id:2434745 TI - Mechanochemical Coupling in the Myosin Motor Domain. II. Analysis of Critical Residues JF - PLoS Computational Biology VL - 3 IS - 2 SP - e23 N2 - An important challenge in the analysis of mechanochemical coupling in molecular motors is to identify residues that dictate the tight coupling between the chemical site and distant structural rearrangements. In this work, a systematic attempt is made to tackle this issue for the conventional myosin. By judiciously combining a range of computational techniques with different approximations and strength, which include targeted molecular dynamics, normal mode analysis, and statistical coupling analysis, we are able to identify a set of important residues and propose their relevant function during the recovery stroke of myosin. These analyses also allowed us to make connections with previous experimental and computational studies in a critical manner. The behavior of the widely used reporter residue, Trp501, in the simulations confirms the concern that its fluorescence does not simply reflect the relay loop conformation or active-site open/close but depends subtly on its microenvironment. The findings in the targeted molecular dynamics and a previous minimum energy path analysis of the recovery stroke have been compared and analyzed, which emphasized the difference and complementarity of the two approaches. In conjunction with our previous studies, the current set of investigations suggest that the modulation of structural flexibility at both the local (e.g., active-site) and domain scales with strategically placed “hotspot” residues and phosphate chemistry is likely the general feature for mechanochemical coupling in many molecular motors. The fundamental strategies of examining both collective and local changes and combining physically motivated methods and informatics-driven techniques are expected to be valuable to the study of other molecular motors and allosteric systems in general. KW - analysis KW - md KW - motor KW - myosin KW - normal-mode AU - Yu, Haibo AU - Ma, Liang AU - Yang, Yang AU - Cui, Qiang PY - 2007/02/01/ UR - http://dx.doi.org/10.1371/journal.pcbi.0030023 ER -