Conformational flexibility and protein folding: rigid structural fragments connected by flexible joints in subtilisin BPN.

Publisher Website
Google Scholar
Abstract
Conformational energy calculations are used to analyze the interactions of structural substructures in subtilisin BPN [Bacillus protease-N]. These substructures are kept fixed or rigid so that the only variables in the calculations are the backbone segments that separate them. The flexible segments are assumed to be free turns. Using this representation of the protein, it is possible to predict a likely order of events along a folding pathway and preferred modes of conformational changes of the native protein. When the native structure is perturbed by moving the substructures apart, it is possible to assess the range of interactions that return the protein, upon energy minimization, to its original conformation. These results suggest an approach to the folding problem based on the piecemeal formation of tertiary structure from smaller prefolded fragments.