Thiol redox biochemistry: insights from computer simulations

Thiol redox chemical reactions play a key role in a variety of physiologicalprocesses, mainly due to the presence of low-molecular-weight thiols and cysteineresidues in proteins involved in catalysis and regulation. Specifically, the subtlesensitivity of thiol reactivity to the environment makes the use of simulationtechniques extremely valuable for obtaining microscopic insights. In this work wereview the application of classical and quantum–mechanical atomistic simulationtools to the investigation of selected relevant issues in thiol redox biochemistry,such as investigations on (1) the protonation state of cysteine in protein, (2)two-electron oxidation of thiols by hydroperoxides, chloramines, and hypochlorousacid, (3) mechanistic and kinetics aspects of the de novo formation of disulfidebonds and thiol−disulfide exchange, (4) formation of sulfenamides, (5) formation ofnitrosothiols and transnitrosation reactions, and (6) one-electron oxidationpathways.