Iterative cluster‐NMA: A tool for generating conformational transitions in proteins
- 6 January 2009
- journal article
- research article
- Published by Wiley in Proteins-Structure Function and Bioinformatics
- Vol. 74 (3), 760-776
- https://doi.org/10.1002/prot.22200
Abstract
Computational models provide insight into the structure–function relationship in proteins. These approaches, especially those based on normal mode analysis, can identify the accessible motion space around a given equilibrium structure. The large magnitude, collective motions identified by these methods are often well aligned with the general direction of the expected conformational transitions. However, these motions cannot realistically be extrapolated beyond the local neighborhood of the starting conformation. In this article, the iterative cluster‐NMA (icNMA) method is presented for traversing the energy landscape from a starting conformation to a desired goal conformation. This is accomplished by allowing the evolving geometry of the intermediate structures to define the local accessible motion space, and thus produce an appropriate displacement. Following the derivation of the icNMA method, a set of sample simulations are performed to probe the robustness of the model. A detailed analysis of β1,4‐galactosyltransferase‐T1 is also given, to highlight many of the capabilities of icNMA. Remarkably, during the transition, a helix is seen to be extended by an additional turn, emphasizing a new unknown role for secondary structures to absorb slack during transitions. The transition pathway for adenylate kinase, which has been frequently studied in the literature, is also discussed. Proteins 2009.Keywords
This publication has 94 references indexed in Scilit:
- Scale-free dynamics and critical phenomena in cortical activityFrontiers in Physiology, 2013
- Close Correspondence between the Motions from Principal Component Analysis of Multiple HIV-1 Protease Structures and Elastic Network ModesStructure, 2008
- Large-scale allosteric conformational transitions of adenylate kinase appear to involve a population-shift mechanismProceedings of the National Academy of Sciences, 2007
- Conformational Transitions of Adenylate Kinase: Switching by CrackingJournal of Molecular Biology, 2006
- Multiple-basin energy landscapes for large-amplitude conformational motions of proteins: Structure-based molecular dynamics simulationsProceedings of the National Academy of Sciences, 2006
- Low-frequency normal modes that describe allosteric transitions in biological nanomachines are robust to sequence variationsProceedings of the National Academy of Sciences, 2006
- The Extent of Cooperativity of Protein Motions Observed with Elastic Network Models Is Similar for Atomic and Coarser-Grained ModelsJournal of Chemical Theory and Computation, 2006
- Normal mode based flexible fitting of high-resolution structure into low-resolution experimental data from cryo-EMJournal of Structural Biology, 2004
- The Protein Data BankNucleic Acids Research, 2000
- CHARMM: A program for macromolecular energy, minimization, and dynamics calculationsJournal of Computational Chemistry, 1983