Hydrogen-bonding— specific-site solvation

Accurate predictions of solute interactions with a limited number of solvent molecules are possible using the supermolecular approximation. This is an approach based on the consideration of the dissolved molecule together with the limited number of solvent molecules as the unified system. The quantum-chemical calculations are performed on the complex of the solute molecule surrounded by as many solvent molecules as possible. The main advantage of the supermolecular approximation is the ability to take into account such specific effects of solvation as hydrogen bonding between the selected sites of the solvated molecules and the molecules of the solvent. In principle there are only two restrictions for the supermolecular approximation. One of them is the internal limitations of the quantum-chemical methods. The second restriction is the limitation of the current computer technology. Because of such restrictions this approximation coupled with ab initio molecular dynamics is possible only for small model systems.46-50... 

A typical globular protein adopts a unique minimum energy conformation that is compact with few or no internal water molecules. Hydrophobic (nonpolar) R groups tend to be on the inside (away from water) and most hydrophilic (polar) R groups tend to be on the outside where they can be solvated by hydrogen bonding with H20. In the case of enzymes (proteins that catalyse specific chemical reactions) there may be special structural features of which the best known are active site depressions or grooves on the surface that bind the chemical substrates of the enzyme-catalysed reaction. 

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