8 - Molecular surfaces and volumes

Abstract

The surface and volume of a molecule represent important parameters involved in various research areas such as intermolecular interactions, drug design, and protein folding. Molecular volume intervenes in many computational approaches of drug design since steric fit is an important feature in the “lock-and-key” or “hand-and-glove” models of molecular interactions involved in pharmacophore recognition. Molecular volume also appears as one of the fundamental properties of macromolecules, directly related to their physicochemical characteristics. Density, for instance, is a useful parameter in the study of the tertiary structure of proteins; its local variations in the interior regions and packing defects have been related to conformational fluctuations, folding, or hydrogen exchange. The external surface represents the interface with the surrounding medium. It gives a first image of the areas able to bind ligands or other macromolecules and to interact with the solvent. Two general approaches have been developed: numerical and analytical. The analytical methods give an exact answer from a set of equations but require somewhat involved geometrical computations. Numerical algorithms subdivide the object into a large number of small elementary similar subunits, for example, elementary cubes or “voxels,” the union of which reproduces the actual object. The method is only approximate but can be efficiently programmed and is very convenient for the logical operations (Boolean operations) involved in the comparison of surfaces or volumes for several neighboring molecules.