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

Kaihsu Tai, Marc Baaden, Stuart Murdock, Bing Wu, Muan Hong Ng, Steven Johnston, Richard Boardman, Hans Fangohr, Katherine Cox, Jonathan W. Essex, Mark S. P. Sansom

Research output: Contribution to journalArticlepeer-review


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.
Original languageEnglish
Pages (from-to)896-902
Number of pages7
JournalJournal of Molecular Graphics and Modelling
Issue number6
Early online date3 Sept 2006
Publication statusPublished - Mar 2007


  • biomolecular simulation
  • database
  • data mining
  • molecular dynamics
  • catalytic triad
  • conformational change


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