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Molecular dynamics in drug design

Authors:
H. Zhao; A. Caflisch

Journal: Eur. J. Med. Chem.
Year: 2015
Volume: 91
Pages: 4-14
DOI: http://dx.doi.org/10.1016/j.ejmech.2014.08.004
Type of Publication: Journal Article

Keywords:
Atomistic simulation; bromodomains; high-throughput docking; In silico screening; Proteases; Tyrosine kinases

Abstract:

Abstract Molecular dynamics (MD) simulations are useful tools for structure-based drug design. We review recent publications in which explicit solvent MD was used at the initial or final stages of high-throughput docking campaigns. In some cases, MD simulations of the protein target have been carried out before docking to generate a conformer of the protein which differs from the available crystal structure(s). Furthermore, MD runs have been performed after docking to assess the predicted binding modes of the top ranking compounds as final filter in silico or to guide chemical synthesis for hit optimization. We present examples of in silico discoveries of tyrosine kinase inhibitors and bromodomain antagonists whose binding mode was predicted by automated docking and further corroborated by MD simulations with final validation by X-ray crystallography.