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Structure-Based Drug Design pp 41–52Cite as

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

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Part of the book series: NATO ASI Series ((NSSE,volume 352))

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.

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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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Authors and Affiliations

  1. European Molecular Biology Laboratory, Meyerhofstr 1, 69012, Heidelberg, Germany

    R. C. Wade & S. Lüdemann

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  1. R. C. Wade
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  2. S. Lüdemann
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Editors and Affiliations

  1. Department of Chemistry, University of Victoria, Victoria, B.C., Canada

    Penelope W. Codding

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Wade, R.C., Lüdemann, S. (1998). Computational Strategies for Modeling Receptor Flexibility in Studies of Receptor-Ligand Interactions. In: Codding, P.W. (eds) Structure-Based Drug Design. NATO ASI Series, vol 352. Springer, Dordrecht. https://doi.org/10.1007/978-94-015-9028-0_4

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  • DOI: https://doi.org/10.1007/978-94-015-9028-0_4

  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-90-481-5078-6

  • Online ISBN: 978-94-015-9028-0

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