Geometry-Based Sampling of Conformational Transitions in Proteins

@article{citeulike:2392665, abstract = {Summary The fast and accurate prediction of protein flexibility is one of the major challenges in protein science. Enzyme activity, signal transduction, and ligand binding are dynamic processes involving essential conformational changes ranging from small side chain fluctuations to reorientations of entire domains. In the present work, we describe a reimplementation of the CONCOORD approach, termed tCONCOORD, which allows a computationally efficient sampling of conformational transitions of a protein based on geometrical considerations. Moreover, it allows for the extraction of the essential degrees of freedom, which, in general, are the biologically relevant ones. The method rests on a reliable estimate of the stability of interactions observed in a starting structure, in particular those interactions that change during a conformational transition. Applications to adenylate kinase, calmodulin, aldose reductase, T4-lysozyme, staphylococcal nuclease, and ubiquitin show that experimentally known conformational transitions are faithfully predicted.}, author = {Seeliger, Daniel and Haas, Jurgen and de Groot, Bert L. }, citeulike-article-id = {2392665}, doi = {10.1016/j.str.2007.09.017}, journal = {Structure}, keywords = {computation, prediction, protein, structure}, month = {November}, number = {11}, pages = {1482--1492}, posted-at = {2008-02-18 07:11:55}, priority = {2}, title = {Geometry-Based Sampling of Conformational Transitions in Proteins}, url = {http://dx.doi.org/10.1016/j.str.2007.09.017}, volume = {15}, year = {2007} }

TY - JOUR ID - citeulike:2392665 L3 - citeulike-article-id:2392665 TI - Geometry-Based Sampling of Conformational Transitions in Proteins JF - Structure VL - 15 IS - 11 SP - 1482 EP - 1492 N2 - Summary The fast and accurate prediction of protein flexibility is one of the major challenges in protein science. Enzyme activity, signal transduction, and ligand binding are dynamic processes involving essential conformational changes ranging from small side chain fluctuations to reorientations of entire domains. In the present work, we describe a reimplementation of the CONCOORD approach, termed tCONCOORD, which allows a computationally efficient sampling of conformational transitions of a protein based on geometrical considerations. Moreover, it allows for the extraction of the essential degrees of freedom, which, in general, are the biologically relevant ones. The method rests on a reliable estimate of the stability of interactions observed in a starting structure, in particular those interactions that change during a conformational transition. Applications to adenylate kinase, calmodulin, aldose reductase, T4-lysozyme, staphylococcal nuclease, and ubiquitin show that experimentally known conformational transitions are faithfully predicted. KW - computation KW - prediction KW - protein KW - structure AU - Seeliger, Daniel AU - Haas, Jurgen AU - de Groot, Bert PY - 2007/11/13/ UR - http://dx.doi.org/10.1016/j.str.2007.09.017 ER -