Computational approaches to amino acid side-chain conformation using combined NMR theoretical and experimental results: leucine-67 in Desulfovibrio vulgaris flavodoxin.

In this paper, we show that the combination of NMR theoretical and experimental results can help to solve the molecular structure of peptides, here it is used as an example the residue Leucine-67 in Desulfovibrio vulgaris flavodoxin. We apply a computational protocol based on the leucine amino acid dipeptide, which, using calculated and experimental spin-spin coupling constants, allows us to obtain the conformation of the amino acid side chain. Calculated results show that the best agreement is obtained when three conformers around the lateral chain angle $\chi _1$ are considered or when the dynamic effect in the torsional angles is included. The population of each structure is estimated and analyzed according to the correlation between those two approaches. Independently of the approach, the estimated $\chi _1$ angle in solution is close to the staggered value of -60$^\circ $ and deviates significantly from the average x-ray angle of -90$^\circ $.

Toward a Computational NMR Procedure for Modeling Dipeptide Side-Chain Conformation.

Theoretical relationships between the vicinal spin-spin coupling constants (SSCCs) and the χ1 torsion angles have been studied to predict the conformations of protein side chains. An efficient computational procedure is developed to obtain the conformation of dipeptides through theoretical and experimental SSCCs, Karplus equations, and quantum chemistry methods, and it is applied to three aliphatic hydrophobic residues (Val, Leu, and Ile). Three models are proposed: unimodal-static, trimodal-static-stepped, and trimodal-static-trigonal, where the most important factors are incorporated (coupled nuclei, nature and orientation of the substituents, and local geometric properties). Our results are validated by comparison with NMR and X-ray empirical data described in the literature, obtaining successful results on the 29 residues considered. Using out trimodal residue treatment, it is possible to detect and resolve residues with a simple conformation and those with two or three staggered conformers. In four residues, a deeper analysis explains that they do not have a unique conformation and that the population of each conformation plays an important role.

Potential energy surface and reactive collisions for the Au+H(2) system.

A global potential energy surface is obtained for the ground state of the endoergic Au((2)S)+H(2)(X (1)Sigma(g) (+))-->AuH((1)Sigma(+))+H((2)S) reaction. The global potential is obtained by fitting highly correlated ab initio calculations on the system, using relativistic pseudopotential for the gold atom. Several electronic states are calculated correlating with Au((2)S)+H(2), Au((2)D)+H(2), and H(2), Au((2)P)+H(2) asymptotes. These states show several conical intersections and curve crossings along the minimum energy reaction path which are analyzed in detail. One of them gives rise to an insertion well in which there are important contributions from the Au((2)D) and Au((2)P) states of gold, which is interesting because it is analog to the deep chemisorption well appearing in larger gold clusters. Quantum wave packet and quasiclassical trajectory dynamical calculations performed for the reaction at zero total angular momentum are in good agreement, provided that a Gaussian binning method is used to account for the zero-point energy of products. Finally, integral and differential cross sections are calculated for the reaction with quasiclassical trajectories. Two different reaction mechanisms are found, one direct and the second indirect, in which the Au atom inserts in between the two hydrogen atoms because of the existence of the insertion well discussed above.

Ionic liquid mixtures--an analysis of their mutual miscibility.

The use of ionic liquid mixtures (IL-IL mixtures) is being investigated for fine solvent properties tuning of the IL-based systems. The scarce available studies, however, evidence a wide variety of mixing behaviors (from almost ideal to strongly nonideal), depending on both the structure of the IL components and the property considered. In fact, the adequate selection of the cations and anions involved in IL-IL mixtures may ensure the absence or presence of two immiscible liquid phases. In this work, a systematic computational study of the mixing behavior of IL-IL systems is developed by means of COSMO-RS methodology. Liquid-liquid equilibrium (LLE) and excess enthalpy (H(E)) data of more than 200 binary IL-IL mixtures (including imidazolium-, pyridinium-, pyrrolidinium-, ammonium-, and phosphonium-based ILs) are calculated at different temperatures, comparing to literature data when available. The role of the interactions between unlike cations and anions on the mutual miscibility/immiscibility of IL-IL mixtures was analyzed. On the basis of proposed guidelines, a new class of immiscible IL-IL mixtures was reported, which only is formed by imidazolium-based compounds.

Computational study of khellin excited states and photobinding to DNA.

A theoretical investigation of the formation and spectroscopic properties of the furan and pyrone monoadducts between the photosensitizer khellin and DNA base thymine is reported. The thermal reaction pathways involve very high barriers, whereas the excited state surfaces display low barriers in regions leading to the ground state TS structures and potential wells at the ground state TS geometries. Computed UV absorption spectra are interpreted with the support of molecular orbital calculations, and the role of solvent effects on the spectra is discussed. The red-shift in the khellin spectra upon intercalation in DNA is excellently reproduced by the computational methodology, as is the solvent induced spectral shift. The data also provides an explanation to why khellin predominantly forms furan monoadducts in DNA, as opposed to the closely related psoralen compounds.