Three hydrolases and a transferase: comparative analysis of active-site dynamics via the BioSimGrid database

Tai, Kaihsu, Baaden, Marc, Murdock, Stuart, Wu, Bing, Ng, Muan Hong, Johnston, Steven, Boardman, Richard, Fangohr, Hans, Cox, Katherine, Essex, Jonathan W. and Sansom, Mark S.P. (2007) Three hydrolases and a transferase: comparative analysis of active-site dynamics via the BioSimGrid database. Journal of Molecular Graphics and Modelling, 25, (6), 896-902. (doi:10.1016/j.jmgm.2006.08.010).


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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 ( 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 ~0.1 µs 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.

Item Type: Article
Digital Object Identifier (DOI): doi:10.1016/j.jmgm.2006.08.010
ISSNs: 1093-3263 (print)
Related URLs:
Keywords: biomolecular simulation, database, data mining, molecular dynamics, catalytic triad, conformational change
Subjects: Q Science > QA Mathematics > QA75 Electronic computers. Computer science
Z Bibliography. Library Science. Information Resources > ZA Information resources > ZA4450 Databases
Q Science > QH Natural history > QH301 Biology
Divisions : University Structure - Pre August 2011 > School of Engineering Sciences > Computational Engineering and Design
ePrint ID: 44165
Accepted Date and Publication Date:
Date Deposited: 19 Feb 2007
Last Modified: 31 Mar 2016 12:17

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