Estimating Relative Disulfide Energies: An Accurate Ab Initio Potential Energy Surface

Abstract

Disulfide torsional energy, a good predictor of disulfide redox potential in proteins, may be estimated by interpolation on a potential energy surface (PES) describing the twisting of diethyl disulfide through its three central dihedral angles. Here we update PES calculations at the M05-2X level of theory with the 6-31G(d) basis set. Although the surface shows no qualitative differences from an earlier MP2(full) PES, energy differences greater than 1 kJ mol–1 were seen for conformations with χ2 between –60° and 30°, or with χ3 below 60° or above 130°. This is particularly significant for highly strained disulfides that are likely to be spontaneously reduced by mechanical means. In benchmarking against the high-level G3X method, M05-2X showed significantly reduced root mean squared deviation compared with MP2(full) (1.0 versus 2.0 kJ mol–1 respectively). Results are incorporated into a web application that calculates relative torsional energies from disulfide dihedral angles (http://www.sbinf.org/applications/pes.html).

Arylsulfanyl radical lifetime in nanostructured silica: dramatic effect of the organic monolayer structure

“…This average value does not t the skew conformation, where the dihedral angle is close to 85 , which is known to be the most stable both experimentally [41][42][43] and theoretically. 36,[49][50][51] Any disulde linkage formed in such a compressed cis conformation would be highly energetic, as stated above. In other words, under this monolayer-like structure the formation of disulde is hindered.…”

Cross-strand disulfides in the non-hydrogen bonding site of antiparallel β-sheet (aCSDns): poised for biological switching

“…(b) Dependence of disulde torsional strain on embeddedness. As in previous works, 11,22,44 we assessed the strain experienced by each aCSDn in our database due to torsion around the dihedral angles of the disulde bond. In particular, we investigated the dependence of the torsional strain of the disulde on the embeddedness of the motif.…”

“…[18][19][20][21] The number of aCSDns in protein structures in the PDB is increasing relative to other disuldes, likely due to the solution of more challenging structures that contain redox-active disuldes as technical advances in X-ray crystallography are made. 22 Several groups have investigated the properties of aCSDns found in the PDB, [23][24][25][26] focussing on the conformations adopted by the disuldes and the associated torsional strain. These investigations have consistently found that aCSDns have an extremely strong preference to adopt a right-handed staple disulde conformation.…”

Molecular Modelling: All the Way from Atomistic Structure to Function in Complex Systems

“…[2] An accurate ab initio potential energy surface describing the twisting of diethyl disulfide through its three central dihedral angles is described by Haworth and coworkers. [3] Zhang and colleagues report a first-principles study of fluorination effects on atomic hydrogen interactions with fluorinated corannulene radical (C 15 H 10 F 5 ). They found that on carbon top site the adsorption is almost barrierless, whereas in the middle bond site there is a barrier for the hydrogen adsorption.…”