WHAT IS THE NATURAL BOUNDARY OF A PROTEIN IN SOLUTION

At what distance do proteins in solution interact? Molecular simulation of water around two helices is used to address this question. Calculations are done with two ideal, parallel, polyalanine α-helices separated by 9 Å, 11 Å, 13 Å, and 15 Å. The second peak in the oxygen density (or loosely the second shell of water molecules) is used to define a hydration surface around the protein, which separates bulk solvent from water molecules strongly influenced by the protein. The hydration surface is contrasted with the Richards-Connolly molecular surface. It indicates that the helices are not completely separate until 15 Å, while the molecular surface shows complete separation at 13 Å. Suggesting shape-dependent aspects of hydration, the hydration surface only loosely follows the van der Waals outline of the protein surface. In particular, at the 9 Å separation, the van der Waals envelopes of the helices make contact; two narrow crevices are formed on either side of the contact; and the water within the crevices is strongly localized in arrangements bridging the helices. A comparison of these ‘normal’ water simulations with a simulation of a simple, uncharged solvent highlights the importance of hydrogen bonding in structuring liquid water and further contrasts the molecular surface and the hydration surface. © 1993 Academic Press Limited.