Ras Conformational Switching: Simulating Nucleotide-Dependent Conformational Transitions with Accelerated Molecular Dynamics Export

@article{citeulike:4199708, abstract = {<title>Author Summary</title> <p>The Ras family of enzymes mediate signaling pathways controlling cell proliferation and development by cycling between active and inactive conformational states. Mutations that affect the ability to switch between states are associated with a variety of cancers. However, details of how the structural changes occur and how mutations affect the fidelity of this process remain to be determined. Here we employ an advanced computational technique, termed accelerated molecular dynamics, to characterize structural transitions and identify novel highly populated transient conformations. Several spatially distant structural regions were found to undergo correlated motions, highlighting a dynamic linkage between the sites of enzymatic reaction and the membrane-interacting C-terminus. In addition, our results indicate that the major motion occurring during the conformational exchange is a low-frequency motion intrinsic to the structure. Hence, features of the characterized transitions likely apply to a large number of structurally similar but functionally diverse nucleotide triphosphatases. These results provide fresh insights into how oncogenic mutations might modulate conformational transitions in Ras.</p>}, author = {Grant, Barry J. and Gorfe, Alemayehu A. and Mccammon, Andrew J.}, citeulike-article-id = {4199708}, citeulike-linkout-0 = {http://dx.doi.org/10.1371/journal.pcbi.1000325}, day = {20}, doi = {10.1371/journal.pcbi.1000325}, journal = {PLoS Comput Biol}, keywords = {accelerated\_md, md\_simulation, protein\_structure, ras}, month = {March}, number = {3}, pages = {e1000325+}, posted-at = {2009-03-20 17:13:40}, priority = {2}, publisher = {Public Library of Science}, title = {Ras Conformational Switching: Simulating Nucleotide-Dependent Conformational Transitions with Accelerated Molecular Dynamics}, url = {http://dx.doi.org/10.1371/journal.pcbi.1000325}, volume = {5}, year = {2009} }

TY - JOUR ID - citeulike:4199708 L3 - citeulike-article-id:4199708 N2 - <title>Author Summary</title> <p>The Ras family of enzymes mediate signaling pathways controlling cell proliferation and development by cycling between active and inactive conformational states. Mutations that affect the ability to switch between states are associated with a variety of cancers. However, details of how the structural changes occur and how mutations affect the fidelity of this process remain to be determined. Here we employ an advanced computational technique, termed accelerated molecular dynamics, to characterize structural transitions and identify novel highly populated transient conformations. Several spatially distant structural regions were found to undergo correlated motions, highlighting a dynamic linkage between the sites of enzymatic reaction and the membrane-interacting C-terminus. In addition, our results indicate that the major motion occurring during the conformational exchange is a low-frequency motion intrinsic to the structure. Hence, features of the characterized transitions likely apply to a large number of structurally similar but functionally diverse nucleotide triphosphatases. These results provide fresh insights into how oncogenic mutations might modulate conformational transitions in Ras.</p> IS - 3 JF - PLoS Comput Biol TI - Ras Conformational Switching: Simulating Nucleotide-Dependent Conformational Transitions with Accelerated Molecular Dynamics PB - Public Library of Science VL - 5 SP - e1000325 KW - accelerated_md KW - md_simulation KW - protein_structure KW - ras AU - Grant, Barry AU - Gorfe, Alemayehu AU - Mccammon, Andrew PY - 2009/03/20/ UR - http://dx.doi.org/10.1371/journal.pcbi.1000325 ER -