STRUCTURAL STABILITY OF DISULFIDE MUTANTS OF BASIC PANCREATIC TRYPSIN-INHIBITOR - A MOLECULAR-DYNAMICS STUDY

The structure and folding of basic pancreatic trypsin inhibitor (BPTI) has been studied extensively by experimental means, We report a compu ter simulation study of the structural stability of various disulfide mutants of BPTI, involving eight 250-psec molecular dynamics simulatio ns of the proteins in water, with and without a phosphate counterion. The presence of the latter alters the relative stability of the single disulfide species [5-55] and [30-51]. This conclusion can explain res ults of mutational studies and the conservation of residues in homolog ues of BPTI, and suggests a possible role of ions in stabilizing one i ntermediate over another in unfolding or folding processes. (C) 1996 W iley-Liss, Inc.