Refined models for computer simulation of protein folding: Applications to the study of conserved secondary structure and flexible hinge points during the folding of pancreatic trypsin inhibitor

摘要: Abstract A new model and parameters are proposed for the computer simulation of protein folding, which satisfy requirements a fully automatic as discussed in recent critical reviews. The were obtained, refined or checked by empirical observations on proteins known sequence conformation, order to avoid much possible theoretical deductions about nature interactions between groups proteins, may not be justified current status art. major improvement over previous methods is retain more realistic complete representation backbone, alternatively reduce number variables coupling their behaviour. As an example, method applied simulate folding pancreatic trypsin inhibitor, leads root-mean-square fit 6·0 with good secondary structure. This also allows detailed examination structure transitions during than has been hitherto. Although, most extensively, advantage initial statistical predictions demonstrated, was free change simulation. from extended chain described, refinements tested. By observing changes simulated it shown that α-helices regions predicted at outset, formed early simulation, conserved, certain residues crucial flexible hinge-points bring together achieve tertiary packing. In view debate importance glycyl hinge-points, danger imparting glycyl-like backbone behaviour non-glycyl suspected considerable interest hinge-point identified us , general, residues. makes important distinction “reverse turn region”, glycine statistically strong candidate, backbone. It reverse turns locally determined likely fairly stable process, while interactions. distinction, implicit papers concerned prediction, made clearly reports simulations.