Understanding Water and Its Many Roles in Biological Structure: Ways to Exploit a Resource for Drug Discovery

Ahmed, Mostafa H.; Amadasi, Alessio; Bayden, Alexander S.; Cashman, Derek J.; Cozzini, Pietro; Da, Chenxiao; Chen, Deliang L.; Fornabaio, Micaela; Kopardé, Vishal N.; Mozzarelli, Andrea; Parikh, Hardik I.; Sarkar, Aurijit; Scarsdale, J.N.; Spyrakis, Francesca; Surface, J. Andrew; Tripathi, Ashutosh; Zaidi, Saheem A.; Kellogg, Glen E.

doi:10.1007/7653_2015_58

Cited by 1 publication

(1 citation statement)

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“…The importance of structured water molecules in biological systems cannot be overstated given their critical roles in modulating protein–ligand interactions, and these considerations take center stage in the context of drug design and discovery [21]. When a structured water molecule is displaced by a ligand and banished to “bulk” solvent, the act of displacement increases system entropy and helps drive ligand binding.…”

Section: Introductionmentioning

confidence: 99%

Molecular Docking: From Lock and Key to Combination Lock

Tripathi

Bankaitis

2018

J Mol Med Clin Appl

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Accurate modeling of protein ligand binding is an important step in structure-based drug design, is a useful starting point for finding new lead compounds or drug candidates. The ‘Lock and Key’ concept of protein-ligand binding has dominated descriptions of these interactions, and has been effectively translated to computational molecular docking approaches. In turn, molecular docking can reveal key elements in protein-ligand interactions-thereby enabling design of potent small molecule inhibitors directed against specific targets. However, accurate predictions of binding pose and energetic remain challenging problems. The last decade has witnessed more sophisticated molecular docking approaches to modeling protein-ligand binding and energetics. However, the complexities that confront accurate modeling of binding phenomena remain formidable. Subtle recognition and discrimination patterns governed by three-dimensional features and microenvironments of the active site play vital roles in consolidating the key intermolecular interactions that mediates ligand binding. Herein, we briefly review contemporary approaches and suggest that future approaches treat protein-ligand docking problems in the context of a ‘combination lock’ system.

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Section: Introductionmentioning

confidence: 99%