The His23 and Lys79 pair determines the high catalytic efficiency of the inorganic pyrophosphatase of the haloacid dehalogenase superfamily

The method of dispersion correction as an add-on to standard Kohn-Sham density functional theory (DFT-D) has been refined regarding higher accuracy, broader range of applicability, and less empiricism. The main new ingredients are atom-pairwise specific dispersion coefficients and cutoff radii that are both computed from first principles. The coefficients for new eighth-order dispersion terms are computed using established recursion relations. System (geometry) dependent information is used for the first time in a DFT-D type approach by employing the new concept of fractional coordination numbers (CN). They are used to interpolate between dispersion coefficients of atoms in different chemical environments. The method only requires adjustment of two global parameters for each density functional, is asymptotically exact for a gas of weakly interacting neutral atoms, and easily allows the computation of atomic forces. Three-body nonadditivity terms are considered. The method has been assessed on standard benchmark sets for inter- and intramolecular noncovalent interactions with a particular emphasis on a consistent description of light and heavy element systems. The mean absolute deviations for the S22 benchmark set of noncovalent interactions for 11 standard density functionals decrease by 15%-40% compared to the previous (already accurate) DFT-D version. Spectacular improvements are found for a tripeptide-folding model and all tested metallic systems. The rectification of the long-range behavior and the use of more accurate C(6) coefficients also lead to a much better description of large (infinite) systems as shown for graphene sheets and the adsorption of benzene on an Ag(111) surface. For graphene it is found that the inclusion of three-body terms substantially (by about 10%) weakens the interlayer binding. We propose the revised DFT-D method as a general tool for the computation of the dispersion energy in molecules and solids of any kind with DFT and related (low-cost) electronic structure methods for large systems.

We announce the release of an advanced version of the Molecular Evolutionary Genetics Analysis (MEGA) software, which currently contains facilities for building sequence alignments, inferring phylogenetic histories, and conducting molecular evolutionary analysis. In version 6.0, MEGA now enables the inference of timetrees, as it implements the RelTime method for estimating divergence times for all branching points in a phylogeny. A new Timetree Wizard in MEGA6 facilitates this timetree inference by providing a graphical user interface (GUI) to specify the phylogeny and calibration constraints step-by-step. This version also contains enhanced algorithms to search for the optimal trees under evolutionary criteria and implements a more advanced memory management that can double the size of sequence data sets to which MEGA can be applied. Both GUI and command-line versions of MEGA6 can be downloaded from www.megasoftware.net free of charge.