Structure-Based Drug Design pp 41-52

Part of the NATO ASI Series book series (NSSE, volume 352) | Cite as

Computational Strategies for Modeling Receptor Flexibility in Studies of Receptor-Ligand Interactions

  • R. C. Wade
  • S. Lüdemann

Abstract

All biomolecular binding processes involve molecular dynamics, even those apparently corresponding to the rigid lock-and-key model. However, while it is becoming increasingly common to treat the flexibility of small ligands explicitly in drug design studies, the flexibility of macromolecular receptors is often ignored. Here, the different types of receptor motions on ligand binding are described and their implications for drug design discussed. Methods to model and simulate receptor dynamics on ligand binding are outlined. Their current usage in the context of structure-based drug design is described.

Abbreviations

BD

Brownian: dynamics

CS

conformational search

EM

energy minimization

MM

molecular mechanics

MC

Monte Carlo

MD

molecular dynamics

nmr

nuclear magnetic resonance

pmf

potential of mean force

QM

quantum mechanics

rmsd

root mean square deviation

SA

simulated annealing

TI

thermodynamic integration

TP

thermodynamic perturbation.

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Copyright information

© Springer Science+Business Media Dordrecht 1998

Authors and Affiliations

  • R. C. Wade
    • 1
  • S. Lüdemann
    • 1
  1. 1.European Molecular Biology LaboratoryHeidelbergGermany

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