Simulations of biomolecule unbinding from protein using DL_POLY

Abstract

This paper briefly reviews the ideas leading to ligand–receptor interaction being a central topic of research in the biological sciences, especially in pharmacology. The simulation methods for studying ligand–receptor interaction dynamically through ligand unbinding are reviewed, together with the analysis methods devised to examine the unbinding trajectory. Examples of applying DL_POLY in these simulations are given; they include retinol unbinding from the retinol-binding protein, and of serotonin and granisetron unbinding from the 5-HT₃ receptor.

Keywords:

• Granisetron
• Molecular recognition
• Molecular dynamics
• Retinol
• Retinol-binding protein
• Serotonin

Acknowledgements

I am grateful to Ole Olsen for the original idea of mutual repulsion, Søren Toxværd, Andrew Hardwick, Ruth Lynden-Bell, Chan Shek Ling, Owen Saxton, Alex Selby, André Juffer, Peter Howe, Wolfgang Rieping and Michael Witty for mathematical discussions, Bill Smith for advice on implementing mutual repulsion on DL_POLY, Simone Melchionne for suggesting the method of adiabatic switching, and Greg McMullan, Jenny Barna, Nick Maclaren, Guy Cormier and Leung Hin-Tak for technical help. I thank the UK Biotechnology and Biological Sciences Research Council for the award of a David Phillips Fellowship, New Hall, Cambridge, for a Research Fellowship, and the Royal Society for the award of a European Science Exchange Programme travel grant, for different parts of this work. Provision of computational resources on the Hitachi SR2201 at the High Performance Computing Facility of the University of Cambridge is gratefully acknowledged.