Generalized QM/MM Force Matching Approach Applied to the 11-cis Protonated Schiff Base Chromophore of Rhodopsin.

We extended a previously developed force matching approach to systems with covalent QM/MM boundaries and describe its user-friendly implementation in the publicly available software package CPMD. We applied this approach to the challenging case of the retinal protonated Schiff base in dark state bovine rhodopsin. We were able to develop a highly accurate force field that is able to capture subtle structural changes within the chromophore that have a pronounced influence on the optical properties.

Photodynamics of Lys+-Trp protein motifs: hydrogen bonds ensure photostability.

Cation-pi interactions such as Lys(+)-Trp, are highly abundant structural motifs in proteins. Both, experimental and theoretical studies of small prototypical gas phase systems, H+Trp, H+Trp x (H2O)n and H+Gly-Trp, indicate such an arrangement as potential hot spot for photodamage and photoinstability. Here, we study the photodynamical properties of a Lys(+)-Trp pair in the protein human serum albumin (HSA) using nonadiabatic mixed time-dependent density functional theory/molecular mechanics simulations (TDDFT/MM).

Intricacies of Describing Weak Interactions Involving Halogen Atoms within Density Functional Theory.

In this work we assess the performance of different dispersion-corrected density functional theory (DFT) approaches (M06, M06-2X, DFT-D3, and DCACP) in reproducing high-level wave function based benchmark calculations on the weakly bound halogen dimers X2···X2 and X2···Ar (for X = F, Cl, Br, and I), as well as the prototype halogen bonded complexes H3CX···OCH2 (X = Cl, Br, I). In spite of the generally good performance of all tested methods for weakly bound systems, their performance for halogen-containing compounds varies largely. We find maximum errors in the energies with respect to the CCSD(T) reference values of 0.

Pushing the frontiers of first-principles based computer simulations of chemical and biological systems.

The Laboratory of Computational Chemistry and Biochemistry is active in the development and application of first-principles based simulations of complex chemical and biochemical phenomena. Here, we review some of our recent efforts in extending these methods to larger systems, longer time scales and increased accuracies. Their versatility is illustrated with a diverse range of applications, ranging from the determination of the gas phase structure of the cyclic decapeptide gramicidin S, to the study of G protein coupled receptors, the interaction of transition metal based anti-cancer agents with protein targets, the mechanism of action of DNA repair enzymes, the role of metal ions in neurodegenerative diseases and the computational design of dye-sensitized solar cells.