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Accelerated Molecular Dynamics in Computational Drug Design

  • Jeff Wereszczynski
  • J. Andrew McCammon
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 819)

Abstract

The method of accelerated molecular dynamics (aMD) has been shown to increase the rate of phase-space sampling in biomolecular simulations. In this chapter, we discuss the theory behind aMD and describe the implementation of two versions: dual-boost and selective aMD. Each method has its practical advantages: dual-boost aMD is useful for increasing sampling of global conformational motions while selective aMD can improve the rate of convergence of free energy calculations. Special emphasis is placed on the use of these methods in computer-aided drug design, and the example of oseltamivir binding to neuraminidase is highlighted for both cases.

Key words

Molecular dynamics Conformational sampling Alchemical free energy transformations 

Notes

Acknowledgments

The work described was supported by Award Number F32GM093581 from the National Institute of General Medical Sciences. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of General Medical Sciences or the National Institutes of Health. Additional support has been provided by the NSF, NIH, HHMI, CTBP, NBCR, and the NSF Supercomputer Centers.

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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Department of Chemistry and Biochemistry, Center for Theoretical Biological PhysicsUniversity of California, San DiegoLa JollaUSA
  2. 2.Howard Hughes Medical Institute, Departmentsof Chemistry and Biochemistry and Pharmacology, Center for Theoretical Biological PhysicsUniversity of California, San DiegoLa JollaUSA

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