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.
BT - European Journal of Medicinal Chemistry C1 - 0194 DA - Feb 16 2015 DO - http://dx.doi.org/10.1016/j.ejmech.2014.08.004 J2 - Eur. J. Med. Chem. LA - eng M3 - Review Article N2 -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.
PY - 2015 SP - 4 EP - 14 T2 - European Journal of Medicinal Chemistry TI - Molecular dynamics in drug design UR - http://www.sciencedirect.com/science/article/pii/S0223523414007314 VL - 91 SN - 0223-5234 ER -