INTRODUCTION

The combination of improved experimental capability, great advances in computer performance, and the development of new algorithms from computer science have led to quite sophisticated methods for the study of certain biomolecules, in particular of folded protein structures. One such technique, called ‘threading,’ picks out small pieces of the primary structure of a protein whose structure is unknown and examines extensive databases of known protein structures to find similar pieces of primary structure. One then guesses that this piece will have the same folded structure as that in the known structure. Since pieces do not all fit together perfectly, an effective force field is used to ‘optimize’ the resultant structure, and Monte Carlo methods have already begun to play a role in this approach. (There are substantial similarities to ‘homology modeling’ approaches to the same, or similar, problems.) Of course, the certainty that the structure is correct comes primarily from comparison with experimental structure determination of crystalized proteins. One limitation is thus that not all proteins can be crystalized, and, even if they can, there is no assurance that the structure will be the same in vivo. Threading algorithms have, in some cases, been extraordinarily successful, but since they do not make use of the interactions between atoms it would be useful to complement this approach by atomistic simulations. (For an introductory overview of protein structure prediction, see Wooley and Ye (2007).) Biological molecules are extremely large and complex; moreover, they are usually surrounded by a large number of water molecules.