Surface Affinity of the Hydronium Ion: The Effective Fragment Potential and Umbrella Sampling

The surface affinity of the hydronium ion in water is investigated with umbrella sampling and classical molecular dynamics simulations, in which the system is described with the effective fragment potential (EFP). The solvated hydronium ion is also explored using second order perturbation theory for the hydronium ion and the empirical TIP5P potential for the waters. Umbrella sampling is used to analyze the surface affinity of the hydronium ion, varying the number of solvent water molecules from 32 to 256. Umbrella sampling with the EFP method predicts the hydronium ion to most probably lie about halfway between the center and edge of the water cluster, independent of the cluster size. Umbrella sampling using MP2 for the hydronium ion and TIP5P for the solvating waters predicts that the solvated proton most probably lies about 0.5–2.0 Å from the edge of the water cluster independent of the cluster size

Efficient and Accurate Fragmentation Methods

Three novel fragmentation methods that are available in the electronic structure program GAMESS (general atomic and molecular electronic structure system) are discussed in this Account. The fragment molecular orbital (FMO) method can be combined with any electronic structure method to perform accurate calculations on large molecular species with no reliance on capping atoms or empirical parameters. The FMO method is highly scalable and can take advantage of massively parallel computer systems. For example, the method has been shown to scale nearly linearly on up to 131 000 processor cores for calculations on large water clusters. There have been many applications of the FMO method to large molecular clusters, to biomolecules (e.g., proteins), and to materials that are used as heterogeneous catalysts. The effective fragment potential (EFP) method is a model potential approach that is fully derived from first principles and has no empirically fitted parameters. Consequently, an EFP can be generated for any molecule by a simple preparatory GAMESS calculation. The EFP method provides accurate descriptions of all types of intermolecular interactions, including Coulombic interactions, polarization/induction, exchange repulsion, dispersion, and charge transfer. The EFP method has been applied successfully to the study of liquid water, π-stacking in substituted benzenes and in DNA base pairs, solvent effects on positive and negative ions, electronic spectra and dynamics, non-adiabatic phenomena in electronic excited states, and nonlinear excited state properties. The effective fragment molecular orbital (EFMO) method is a merger of the FMO and EFP methods, in which interfragment interactions are described by the EFP potential, rather than the less accurate electrostatic potential. The use of EFP in this manner facilitates the use of a smaller value for the distance cut-off (Rcut). Rcut determines the distance at which EFP interactions replace fully quantum mechanical calculations on fragment–fragment (dimer) interactions. The EFMO method is both more accurate and more computationally efficient than the most commonly used FMO implementation (FMO2), in which all dimers are explicitly included in the calculation. While the FMO2 method itself does not incorporate three-body interactions, such interactions are included in the EFMO method via the EFP self-consistent induction term. Several applications (ranging from clusters to proteins) of the three methods are discussed to demonstrate their efficacy. The EFMO method will be especially exciting once the analytic gradients have been completed, because this will allow geometry optimizations, the prediction of vibrational spectra, reaction path following, and molecular dynamics simulations using the method

Recent Developments in the General Atomic and Molecular Electronic Structure System

A discussion of many of the recently implemented features of GAMESS (General Atomic and Molecular Electronic Structure System) and LibCChem (the C++ CPU/GPU library associated with GAMESS) is presented. These features include fragmentation methods such as the fragment molecular orbital, effective fragment potential and effective fragment molecular orbital methods, hybrid MPI/OpenMP approaches to Hartree-Fock, and resolution of the identity second order perturbation theory. Many new coupled cluster theory methods have been implemented in GAMESS, as have multiple levels of density functional/tight binding theory. The role of accelerators, especially graphical processing units, is discussed in the context of the new features of LibCChem, as it is the associated problem of power consumption as the power of computers increases dramatically. The process by which a complex program suite such as GAMESS is maintained and developed is considered. Future developments are briefly summarized

Escherichia coli genome-wide promoter analysis: Identification of additional AtoC binding target elements

<p>Abstract</p> <p>Background</p> <p>Studies on bacterial signal transduction systems have revealed complex networks of functional interactions, where the response regulators play a pivotal role. The AtoSC system of <it>E. coli </it>activates the expression of <it>atoDAEB </it>operon genes, and the subsequent catabolism of short-chain fatty acids, upon acetoacetate induction. Transcriptome and phenotypic analyses suggested that <it>atoSC </it>is also involved in several other cellular activities, although we have recently reported a palindromic repeat within the <it>atoDAEB </it>promoter as the single, <it>cis</it>-regulatory binding site of the AtoC response regulator. In this work, we used a computational approach to explore the presence of yet unidentified AtoC binding sites within other parts of the <it>E. coli </it>genome.</p> <p>Results</p> <p>Through the implementation of a computational <it>de novo </it>motif detection workflow, a set of candidate motifs was generated, representing putative AtoC binding targets within the <it>E. coli </it>genome. In order to assess the biological relevance of the motifs and to select for experimental validation of those sequences related robustly with distinct cellular functions, we implemented a novel approach that applies Gene Ontology Term Analysis to the motif hits and selected those that were qualified through this procedure. The computational results were validated using Chromatin Immunoprecipitation assays to assess the <it>in vivo </it>binding of AtoC to the predicted sites. This process verified twenty-two additional AtoC binding sites, located not only within intergenic regions, but also within gene-encoding sequences.</p> <p>Conclusions</p> <p>This study, by tracing a number of putative AtoC binding sites, has indicated an AtoC-related cross-regulatory function. This highlights the significance of computational genome-wide approaches in elucidating complex patterns of bacterial cell regulation.</p