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 computer simulation study of the structural stability of various disulfide mutants of BPTI, involving eight 250-psec molecular dynamics simulations 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 results of mutational studies and the conservation of residues in homologues of BPTI, and suggests a possible role of ions in stabilizing one intermediate over another in unfolding or folding processes.
Schiffer
C A
CA
Laboratory of Physical Chemistry, ETH-Zentrum, Zürich, Switzerland.
van Gunsteren
W F
WF
D007611:Aprotinin / Q000737:chemistry* / Q000235:genetics; D003198:Computer Simulation; D003461:Crystallography; D004220:Disulfides / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D009154:Mutation / Q000235:genetics; D010710:Phosphates / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D017510:Protein Folding
D004220:Disulfides; D010710:Phosphates; D007611:Aprotinin