Weak nonbonded S•••X (X=O, N, and S) interactions in proteins.: Statistical and theoretical studies.

Sulfur-containing functional groups of cystine (an SSC group) and methionine (a CSC group) are usually considered as hydrophobic moieties or weak hydrogen-bond acceptors in folded protein structures. However, database analysis as well as theoretical calculations carried out in this study have provided strong evidence for the presence of specific non-bonded interactions between the divalent sulfur atoms (S) and nearby polar non-hydrogen atoms (X). Close S...X (X = O, N, S, C, etc.) atomic contacts were statistically analyzed in 604 high-resolution heterogeneous X-ray structures selected from a protein databank (PDB_SELECT). The S...O interactions found for both SSC and CSC groups showed a specific character as a pi(C=O) --> sigma*(S) orbital interaction based on the directional preferences. The interactions were most frequently observed in alpha-helices. Ab initio calculations applying the second order Moller-Plesset perturbation theory (MP2) suggested the primary importance of electron correlations. The total stabilization energies were calculated to be similar to3.2 and similar to2.5 kcal/mol for SSC and CSC groups, respectively, including the contribution from a coexisting CH...O hydrogen bond. On the other hand, the S...N interactions observed for a CSC group exhibited structural characters as a pi(N) --> sigma*(S) orbital interaction and an NH...S hydrogen bond, and the S...S interactions for an SSC group showed a structural character as an n(S) --> sigma*(S) orbital interaction. The S...C(pi) interactions should be rather weak and long-range.