2,372 research outputs found

    The Poisson-Boltzmann model for implicit solvation of electrolyte solutions: Quantum chemical implementation and assessment via Sechenov coefficients.

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    We present the theory and implementation of a Poisson-Boltzmann implicit solvation model for electrolyte solutions. This model can be combined with arbitrary electronic structure methods that provide an accurate charge density of the solute. A hierarchy of approximations for this model includes a linear approximation for weak electrostatic potentials, finite size of the mobile electrolyte ions, and a Stern-layer correction. Recasting the Poisson-Boltzmann equations into Euler-Lagrange equations then significantly simplifies the derivation of the free energy of solvation for these approximate models. The parameters of the model are either fit directly to experimental observables-e.g., the finite ion size-or optimized for agreement with experimental results. Experimental data for this optimization are available in the form of Sechenov coefficients that describe the linear dependence of the salting-out effect of solutes with respect to the electrolyte concentration. In the final part, we rationalize the qualitative disagreement of the finite ion size modification to the Poisson-Boltzmann model with experimental observations by taking into account the electrolyte concentration dependence of the Stern layer. A route toward a revised model that captures the experimental observations while including the finite ion size effects is then outlined. This implementation paves the way for the study of electrochemical and electrocatalytic processes of molecules and cluster models with accurate electronic structure methods

    The AFLOW Fleet for Materials Discovery

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    The traditional paradigm for materials discovery has been recently expanded to incorporate substantial data driven research. With the intent to accelerate the development and the deployment of new technologies, the AFLOW Fleet for computational materials design automates high-throughput first principles calculations, and provides tools for data verification and dissemination for a broad community of users. AFLOW incorporates different computational modules to robustly determine thermodynamic stability, electronic band structures, vibrational dispersions, thermo-mechanical properties and more. The AFLOW data repository is publicly accessible online at aflow.org, with more than 1.7 million materials entries and a panoply of queryable computed properties. Tools to programmatically search and process the data, as well as to perform online machine learning predictions, are also available.Comment: 14 pages, 8 figure

    A THEORETICAL INVESTIGATION EXAMINING DNA CONFORMATIONAL CHANGES AND THEIR EFFECTS ON GLYCOSYLASE FUNCTION

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    Glycosylase enzymes initiate the process of base excision repair (BER) in order to prevent the irreversible modification of the genome. In the BER process a damaged DNA base is recognized, removed from the DNA sequence, and then the remaining abasic site is repaired. Glycosylase enzymes are responsible for the base recognition mechanism and catalysis of the base excision. One of the most studied glycosylase superfamilies is uracil DNA glycosylase (UDG). The UDG superfamily has demonstrated specificity for excising uracil, which is the deamination product of cytosine, from DNA sequences of prokaryotes and eukaryotes. Mismatch-specific uracil DNA glycosylase (MUG) is a member of the UDG superfamily, and interestingly has shown specificity for both uracil and xanthine bases. The following dissertation provides an anlaysis on the recognition mechanism of E. coli MUG for deaminated DNA bases. Glycosylase enzymes require the damaged base to be flipped out of the base stack, and into an active site for catalysis of the N-glycosidic cleavage. Typically, recognition of substrates by enzymes is characterized by binding affinities, but in the following work the binding of E.Coli MUG is broken down into contributions from the base flipping and enzyme binding equilibria. Since DNA conformational changes play a large role in UDG systems, the robustness of molecular mechanics Poisson-Boltzmann surface area (MM/PBSA) free energy method was evaluated for a DNA conformational change. The A-form to B-form DNA conformational free energy differences were calculated using MM/PBSA, and compared with free energy differences determined with a more rigorous umbrella sampling method. MM/PBSA calculations of the free energy difference between A-form and B-form DNA are shown to be in very close agreement with the PMF result determined using an umbrella sampling approach. The sensitivity to solvent model and force field used during conformational sampling was also established for the MM/PBSA free energies. In order to determine the influence of base flipping conformational changes on the MUG recognition process, PMF profiles were generated for each of the damaged bases (uracil, xanthine, oxanine, inosine). Agreement was displayed between the base pair stability trends from the umbrella sampling, and the enzyme activities from experiment. Interaction energies and structural analyses were used to examine the MUG enzyme, which revealed regions of the active site critical for binding xanthine and uracil substrates. Site-directed mutagenesis experiments were performed on MUG to determine the role of specific amino acids in the recognition mechanism. Mutations were studied further through modeling and molecular dynamics (MD) simulations of the unbound and bound proteins
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