Self-Consistent Charge Density Functional Tight Binding (SCC-DFTB) is a semi-empirical method based on Density Functional Theory, and has in many cases been shown to provide relative energies and geometries comparable in accuracy to full DFT or ab-initio MP2 calculations using large basis sets. This article shows an implementation of the SCC-DFTB method as part of the new QM/MM support in the AMBER 9 molecular dynamics program suite. Details of the implementation and examples of applications are shown.

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The PUPIL package (Program for User Package Interfacing and Linking) originally was developed to interface different programs for multiscale calculations in materials sciences (Torras et al., J Comput Aided Mater Des 2006, 13, 201; Torras et al., Comput Phys Commun 2007, 177, 265). Here we present an extension of PUPIL to computational chemistry by interfacing two widely used computational chemistry programs: AMBER (molecular dynamics) and Gaussian (quantum chemistry). The benefit is to allow the application of the advanced MD techniques available in AMBER to a hybrid QM/MM system in which the forces and energy on the QM part can be computed by any of the methods available in Gaussian. To illustrate, we present two example applications: A MD calculation of alanine dipeptide in explicit water, and a use of the steered MD capabilities in AMBER to calculate the free energy of reaction for the dissociation of Angeli's salt.

The quantification of chemical diversity has many applications in drug discovery, organic chemistry, food, and natural product chemistry, to name a few. As the size of the chemical space is expanding rapidly, it is imperative to develop efficient methods to quantify the diversity of large and ultralarge chemical libraries and visualize their mutual relationships in chemical space. Herein, we show an application of our recently introduced extended similarity indices to measure the fingerprint-based diversity of 19 chemical libraries typically used in drug discovery and natural products research with over 18 million compounds. Based on this concept, we introduce the Chemical Library Networks (CLNs) as a general and efficient framework to represent visually the chemical space of large chemical libraries providing a global perspective of the relation between the libraries. For the 19 compound libraries explored in this work, it was found that the (extended) Tanimoto index offers the best description of extended similarity in combination with RDKit fingerprints. CLNs are general and can be explored with any structure representation and similarity coefficient for large chemical libraries.

Together with ionization potentials, cross sections provide valuable information for the interpretation of photoelectron spectra. We have developed a program to perform ab initio calculations of photoionization cross sections within the electric dipole approximation using electron propagator theory. Applications to the first-row hydrides CH(4), NH(3), H(2)O, and HF, using several approximations for the propagator self-energy and the plane-wave and orthogonalized-plane-wave approximations to represent the photoelectron, as well as comparison to experimental data, are presented. This program is implemented within the quantum chemistry package GAUSSIAN.

Heparanase (HPA) is a critical enzyme involved in the remodeling of the extracellular matrix (ECM), and its elevated expression has been linked with diseases such as various types of cancer...

The semiempirical Hamiltonians MNDO, AM1, PM3, RM1, PDDG/MNDO, PDDG/PM3, and SCC-DFTB, when used as part of a hybrid QM/MM scheme for the simulation of biological molecules, were compared on their abilities to reproduce experimental ensemble averages at or near room temperatures for the model system alanine dipeptide in water. Free energy surfaces in the (φ, ψ) dihedral angle space, 3 J(H N ,H R ) NMR dipolar coupling constants, basin populations, and peptide-water radial distribution functions (RDF) were calculated from replica exchange simulations and compared to both experiment and fully classical force field calculations using the Amber ff99SB force field. In contrast with the computational chemist's intuitive idea that the more expensive a method the better its accuracy, the ff99SB force field results were more accurate than most of the semiempirical methods, with the exception of RM1. None of the methods, however, was able to accurately reproduce the experimental data. Analysis of the results indicate that the specific QM/MM interactions have little influence on the sampling of free energy surfaces, and the differences are well explained simply by the intrinsic properties of the various QM methods.

Corrections to dipole approximation results for angular distributions in photoionization of first-row hydrides have determined by using Dyson orbitals calculated with ab initio electron propagator theory and by considering the full multipole expansion for the incident photon representation. The relative importance of first-order corrections which consist of electric quadrupole and magnetic dipole terms and of higher-order terms has been estimated as a function of photon energy. Multipole corrections to the dipole approximation depend on photon energy and on the characteristics of the Dyson orbitals.