Journal
JOURNAL OF MOLECULAR GRAPHICS & MODELLING
Volume 25, Issue 6, Pages 896-902Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jmgm.2006.08.010
Keywords
biomolecular simulation; database; data mining; molecular dynamics; catalytic triad; conformational change
Categories
Funding
- Biotechnology and Biological Sciences Research Council [BBS/B/16011, B19456, BEP17032] Funding Source: Medline
- Biotechnology and Biological Sciences Research Council [BEP17032, B19456, BBS/B/16011] Funding Source: researchfish
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Comparative molecular dynamics (MD) simulations enable us to explore the conformational dynamics of the active sites of distantly related enzymes. We have used the BioSimGrid (http://www.biosimgrid.org) database to facilitate such a comparison. Simulations of four enzymes were analyzed. These included three hydrolases and a transferase, namely acetylcholinesterase, outer-membrane phospholipase A, outer-membrane protease T, and PagP (an outer-membrane enzyme which transfers a palmitate chain from a phospholipid to lipid A). A set of 17 simulations were analyzed corresponding to a total of similar to 0.1 mu s simulation time. A simple metric for active-site integrity was used to demonstrate the existence of clusters of dynamic conformational behaviour of the active sites. Small (i.e. within a cluster) fluctuations appear to be related to the function of an enzymatically active site. Larger fluctuations (i.e. between clusters) correlate with transitions between catalytically active and inactive states. Overall, these results demonstrate the potential of a comparative MD approach to analysis of enzyme function. This approach could be extended to a wider range of enzymes using current high throughput MD simulation and database methods. (c) 2006 Elsevier Inc. All rights reserved.
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