Molecular modelling of conformational changes in solvated alpha(s1)-caseinpeptides

Computer models of alpha(s1)-casein peptides were simulated in an aqueous e nvironment to compare their conformations as separate peptides with structu ral features of corresponding regions in the intact alpha(s1)-casein molecu lar model. Peptide sequences selected for investigation were based on sites of potential cleavage by chymosin and/or plasmin. Four large peptides and several smaller peptide fragments were refined by applying a series of mole cular dynamics simulations and energy minimizations. Most peptides adopted conformations that were more compact than the conformations of the correspo nding sequences in the intact alpha(s1)-casein model. The results indicated that sequences in the peptides that promote the open, flexible structure o f the parent protein are likely to resist formation of new secondary struct ure during refinement. However, these regions can develop more local flexib ility and additional turns because of the high proline content of alpha(s1) -casein. The region in which seven of the eight phosphoserine residues are located maintained its conformation throughout the refinement, but this reg ion adopted a new conformation when phosphoserines were replaced with serin es. The results demonstrate the potential for folding in casein peptides an d highlight the features that promote the open, extended structures of the caseins. Published by Elsevier Science Ltd.