CONFORMATIONAL ENERGY MINIMIZATION IN THE APPROXIMATION OF LIMITED RANGE INTERACTIONS

A general method to determine the conformational free energy minimum is developed by approximating the total molecular free energy as the sum of contributions from independent segments, each of which can exist in several conformations. The simple algorithm to determine the best overall conformation rigorously yields the same results as those obtained by enumerating all possible combinations of independent segments. However, the method, based upon dynamic programming concepts, is much simpler because it avoids explicit generation of all possible combinations of segments. Application of the method to protein secondary structures is discussed. Development of this conformational selection scheme is independent of the method by which free energies have been calculated. An example is presented for determining relative preferences for α-helix and β-strand in a fragment of trypsin inhibitor. © 1979, American Chemical Society. All rights reserved.