Modified self-consistent harmonic approach to thermal fluctuational disruption of disulfide bonds in proteins.
Disulfide bonds (covalent bonds between two sulfur atoms on separate amino acid cysteines) play an important role in the folding stability of many proteins. The determination of the dynamic stability of disulfide bonds can therefore facilitate an understanding of the mechanism of protein stability. We have examined whether a modified self-consistent harmonic approach, which has been successful in modeling hydrogen bond breaking dynamics in DNA and covalent bond disruption in drug-DNA systems, is useful in computing thermal fluctuational disruption probability of disulfide bonds in proteins. Our results on a number of protein x-ray crystal structures showed that the computed disruption probabilities are consistent with observations. The free energies derived from computed probabilities are comparable to the observed values from protein engineering experiments. The method presented here has a potential application in analyzing disulfide bond dynamics in a variety of biological processes.
Chen
Y Z
YZ
Department of Computational Science, National University of Singapore, Lower Kent Ridge Road, Singapore 119260.
D000465:Algorithms; D000818:Animals; D007611:Aprotinin / Q000737:chemistry; D002417:Cattle; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004220:Disulfides / Q000737:chemistry; D007768:Lactalbumin / Q000737:chemistry; D008956:Models, Chemical; D008958:Models, Molecular; D015233:Models, Statistical; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry*; D006163:Ribonuclease T1 / Q000737:chemistry; D012259:Ribonuclease, Pancreatic / Q000737:chemistry; D013816:Thermodynamics
D004220:Disulfides; D011506:Proteins; D007768:Lactalbumin; D007611:Aprotinin; D006163:Ribonuclease T1; D012259:Ribonuclease, Pancreatic