Three hydrolases and a transferase: Comparative analysis of active-site dynamics via the BioSimGrid database - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Journal of Molecular Graphics and Modelling Année : 2007

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

Kaihsu Tai
  • Fonction : Auteur
Marc Baaden
Stuart Murdock
  • Fonction : Auteur
Bing Wu
  • Fonction : Auteur
Muan Hong Ng
  • Fonction : Auteur
Hans Fangohr
  • Fonction : Auteur
Katherine Cox
  • Fonction : Auteur
Mark Sansom
  • Fonction : Auteur
Mark S.P. Sansom
  • Fonction : Auteur

Résumé

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 approximately 0.1 micros 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.

Domaines

Chimie

Dates et versions

hal-03905209 , version 1 (18-12-2022)

Identifiants

Citer

Kaihsu Tai, Marc Baaden, Stuart Murdock, Bing Wu, Muan Hong Ng, et al.. Three hydrolases and a transferase: Comparative analysis of active-site dynamics via the BioSimGrid database. Journal of Molecular Graphics and Modelling, 2007, 25 (6), pp.896-902. ⟨10.1016/j.jmgm.2006.08.010⟩. ⟨hal-03905209⟩
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