24 February 2007

[07.1] J Mol Graph Model. 2007 Mar;25(6):896-902. (Epub 2006 Sep 3)

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

Kaihsu Tai1, Marc Baaden 2, Stuart Murdock3, Bing Wu1, Muan Hong Ng4, Steven Johnston3,4, Richard Boardman3,4, Hans Fangohr4, Katherine Cox1, Jonathan W. Essex3, Mark S. P. Sansom 1,*


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 ~0.1 ms 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.


Correspondence should be addressed to M.S.P. Sansom.

  1. Univ of Oxford, Lab. of Molecular Biophysics, South Parks Road, OX1 3QU Oxford, United Kingdom.
  2. Institut de Biologie Physico-Chimique, Laboratoire de Biochimie Théorique, 13, rue Pierre et Marie Curie, F-75005 Paris, France.
  3. School of Chemistry, University of Southampton, Highfield, Southampton SO17 1BJ, United Kingdom
  4. School of Engineering Science, University of Southampton, Highfield, Southampton SO17 1BJ, United Kingdom

© 2001-2006    Marc Baaden, baaden@smplinux.de