Defelipe, L.A.; Arcon, J.P.; Modenutti, C.P.; Marti, M.A.; Turjanski, A.G.; Barril, X. Solvents to Fragments to Drugs: MD Applications in Drug Design. Molecules2018, 23, 3269.
Defelipe, L.A.; Arcon, J.P.; Modenutti, C.P.; Marti, M.A.; Turjanski, A.G.; Barril, X. Solvents to Fragments to Drugs: MD Applications in Drug Design. Molecules 2018, 23, 3269.
Molecular dynamics(MD) simulations are playing an increasingly important role in structure-based drug discovery (SBDD). Here we review the use of MD for proteins in aqueous solvation, organic/aqueous mixed solvents (MDmix) and with small ligands, to the classic SBDD problems: binding mode and binding free energy predictions. The simulation of proteins in their condensed state reveals the solvent structure and preferential interaction sites (hot spots) on the protein surface. This information is largely transferable across all classes of protein ligands (from water to drugs) and can be used very effectively to understand ligand recognition and improve the predictive capability of well-established methods such as molecular docking. MD simulations for protein and drug or drug-like compounds are now being used but are still computationally expensive and can only be applied to specific cases. On the other hand, MDmix simulations can now be used in SBDD and we will describe the latest developments and implementations. We expect to see an increase in the application of these techniques to a plethora of protein targets to identify new drug candidates with the advent of new tools and faster computers.
Molecular Dynamics, CoSolvent Molecular Dynamics, Drug design, Fragment Screening, Docking
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