Current and emerging opportunities for molecular simulations in structure-based drug design.
An overview of the current capabilities and limitations of molecular simulation of biomolecular complexes in the context of computer-aided drug design is provided. Steady improvements in computer hardware coupled with more refined representations of energetics are leading to a new appreciation of the driving forces of molecular recognition. Molecular simulations are poised to more frequently guide the interpretation of biophysical measurements of biomolecular complexes. Ligand design strategies emerge from detailed analyses of computed structural ensembles. The feasibility of routine applications to ligand optimization problems hinges upon successful extensive large scale validation studies and the development of protocols to intelligently automate computations.
EaStCHEM School of Chemistry, Joseph Black Building, The King's Buildings, Edinburgh, EH9 3JJ, UK. mail@julienmichel.net.
Julien
J
Michel
D017076:Computer-Aided Design; D018360:Crystallography, X-Ray; D015195:Drug Design; D019277:Entropy; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism
D008024:Ligands; D011506:Proteins