Abstract
Hydration has a significant impact on ligand binding within protein active sites. Specific water molecules and their placement within protein active sites have been shown to make specific contributions to the energetics of protein–ligand binding and need consideration in the design of efficient binding ligands. These specific nonbulk water molecules and their interactions are different and have more significant impact in ligand design than the generalized bulk solvation of ligand–protein systems. Proper theoretical description of the solvation effects of water within a ligand-binding pocket is a significant computational challenge. Recently, new computational methods have been developed which can more accurately describe the contribution of waters within a protein ligand site and lead to improved and enhanced ligand design and ranking in computational docking and to greater enrichment.
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Abbreviations
- RISM:
-
Reference interaction site model
- IFST/IST:
-
Inhomogeneous fluid solvation theory
- HFE:
-
Hydration free energy
- MM-PB/SA:
-
Molecular mechanics-poisson-boltzmann/surface area
- MM-GB/SA:
-
Molecular mechanics-generalized born method/surface area
- FEP:
-
Free energy perturbation
- TIP:
-
Transferable interaction potential
- MD:
-
Molecular dynamics
- IETs:
-
Integral equation theories
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Bienstock, R.J. (2015). Solvation Methods for Protein–Ligand Docking. In: Klon, A. (eds) Fragment-Based Methods in Drug Discovery. Methods in Molecular Biology, vol 1289. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-2486-8_1
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DOI: https://doi.org/10.1007/978-1-4939-2486-8_1
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