Molecular dynamics simulations have been performed on the lipase B from Candida antarctica (CalB) in its native form and with one or two oxidized residues, either methionine oxidized to methionine sulfoxide, tryptophan oxidized to 5-hydroxytryptophan, or cysteine oxidized to a pair of cysteic acid residues (twelve simulations in total). The oxidized amino acids were selected from a mass spectrometry-based investigation, showing which amino acids are most prone to be oxidized.We have analyzed how these mutations affect the general structure of the protein, as well as the local structure around the oxidized amino acids and the active site.The results indicate that the methionine and tryptophan oxidations led to rather restricted changes in the structure, whereas the oxidation of cysteines, which also caused cleavage of the cysteine S–S linkage, gave rise to larger changes in the protein structure. Only two oxidized residues caused significant changes in the structure of the active site, viz., those of the Cys-22/64 and Cys-216/258 pairs. We have also looked at the hydrogen-bond structure around the oxidized residues, showing that the new polar atoms that arise through the oxidation often form hydrogen bonds with the surroundings, especially if the residues are solvent exposed.
