Molecular dynamics simulation of the solution structure of the C‐terminal fragment of L7/L12 ribosomal protein

T h e extent of conformational differences between crystal and solution structures of proteins is a n interesting issue that, with the recent progress in two-dimensional nmr struct,ure determination methods, is now becoming possible to elucidate experimentally.'-:'It is generally believed that the effects of the crystal environment on the protein conformation are fairly small (see, e.g., the discussion in Ref. 4 ) .This is based on the fact that protein crystals contain substantial amounts of water and that intermolecular protein-protein contacts in the crystals mostly involve rather limited regions of the molecular surfaces, as compared to, e.g., subunit interactions.In the cases of lysozyme" and subtilisin,' for instance, it has been possible to directly compare x-ray structures from different crystal forms thereby allowing for a n assessment of the magnitude of' crystal packing effects.For chymotrypsin, the differences between independent monomers in the asymmetric unit have been e ~a m i n e d .~ These data suggest that such conformational changes are in general small and that the protein backbone structure is largely unaffected, while changes in the conformation of side chains can result from the particular packing.Molecular dynamics ( MD ) simulation provides a feasible, although computationally expensive, theoretical approach for examining the conformation of a protein in aqueous solution.This type of calculations can also provide detailed information on dynamical properties that is difficult t o ohtain b y other methods.A fundamental question in this context is, of course, the degree of accuracy that can be attained in protein MD simulations.A high accuracy in predicting structural effects will clearly be a requirement when applying M D calculations to problems related to, e g , niutagenesis experiments and drug design.Due to the very substantial computational effort that has t o be invested in simulating the dynamics of a protein surrounded by a large number of water molecules (on the order o f several thousands, depending on the size of the protein) only a few such studies have been reported to C: 1990 .