Sándor Lovas

Calculation of weakly polar interaction energies in polypeptides using density functional and local Møller-Plesset perturbation theory.

The interaction energies of ubiquitous weakly polar interactions in proteins are comparable with those of hydrogen bonds, consequently, they stabilize local, secondary, and tertiary structures. However, the most widely‐used density functionals fail to describe the weakly polar interactions. Thus, it is important to find and test functionals which adequately describe and quantify the energetics of such interactions. For this purpose, interaction energies in the hydrophobic core of rubredoxin (PDB id: 1rb9) and in the S22 subset of the JSCH‐2005 benchmark database were computed with the BHandHLYP and PWPW91 functionals and with the pseudospectral implementation of the local MP2 (PS‐LMP2) method. The cc‐pVDZ, cc‐pVTZ(‐f), cc‐pVTZ, cc‐pVQZ(‐g), aug‐cc‐pVDZ, aug‐cc‐VTZ(‐f), and aug‐cc‐pVTZ basis sets were used for the calculations. In the S22 subset the PS‐LMP2 results were extrapolated to the complete basis set limit. Furthermore, the a posteriori counterpoise method of Boys and Bernardi was used to correct the basis set superposition errors in the calculation of interaction energies. Calculations using the BHandHLYP functional, both for the various weakly polar interactions in rubredoxin and for the dispersion interactions in the S22 subset, were in good agreement with those using the coupled cluster (CCSD(T)) and the resolution of identity MP2 (RIMP2) methods and clearly outperformed both the PWPW91 functional and the PS‐LMP2 method. The results for the S22 hydrogen bonded subset, obtained with PWPW91 calculations, were closest to those of the reference high level calculations. For the “mixed” (hydrogen bonded and dispersive) interactions in the S22 subset, results obtained with the BHandHLYP and PS‐LMP2 calculations agreed well with the reference calculations.

The effect of electron correlation on the conformational space of melatonin

The pineal gland hormone melatonin regulates several physiological processes including circadian rhythm and also alleviates oxidative stress‐induced degenerative diseases. In spite of its important biological roles, no high level ab initio conformational study has been conducted to reveal its structural features. In this work, the conformational flexibility of melatonin was investigated using correlated ab initio calculations. Conformers, obtained previously at the Hartree‐Fock level (HF/6‐31G*), were fully optimized using second order Møller‐Plesset perturbation theory applying the frozen core approximation (MP2(FC)/6‐31G*). Furthermore, single‐point MP4(SDQ,FC)/6‐31G*//MP2(FC)/6‐31G* computations were performed to investigate the effect of higher order perturbation terms. The HF and MP2 conformational spaces are considerably different: the initial 128 structures converged into 102 different local minima as confirmed by frequency calculations; 28 new minima appeared and 26 previous HF local minima disappeared; no “all‐trans” C3 side chain conformations are seen at the MP2(FC) level. The MP2 global minimum conformation is stabilized by an aromatic‐side chain interaction.

The role of weakly polar and H-bonding interactions in the stabilization of the conformers of FGG, WGG, and YGG: An aqueous phase computational study

The energetics of intramolecular interactions on the conformational potential energy surface of the terminally protected N-Ac-Phe-Gly-Gly-NHMe (FGG), N-Ac-Trp-Gly-Gly-NHMe (WGG), and N-Ac-Tyr-Gly-Gly-NHMe (YGG) tripeptides was investigated. To identify the representative conformations, simulated annealing molecular dynamics (MD) and density functional theory (DFT) methods were used. The interaction energies were calculated at the BHandHLYP/aug-cc-pVTZ level of theory. In the global minima, 10%, 31%, and 10% of the stabilization energy come from weakly polar interactions, respectively, in FGG, WGG, and YGG. In the prominent cases 46%, 62%, and 46% of the stabilization energy is from the weakly polar interactions, respectively, in FGG, WGG, and YGG. On average, weakly polar interactions account for 15%, 34%, and 9% of the stabilization energies of the FGG, WGG, and YGG conformers, respectively. Thus, weakly polar interactions can make an important energetic contribution to protein structure and function.