Calculation of Alkane to Water Solvation Free Energies Using Continuum Solvent Models

Abstract

The FDPB/γ method and the PARSE parameter set have been recently shown to provide a computationally efficient and accurate means of calculating hydration free energies. In this paper this approach is extended to the treatment of the partitioning of various solute molecules between the gas phase, water, and alkane solvents. The FDPB/γ method treats the solute molecule as a polarizable cavity embedded in a dielectric continuum. The solute charge distribution is described in terms of point charges located at atomic nuclei. Electrostatic free energies are obtained from numerical (finite difference) solutions to the Poisson (or Poisson−Boltzmann) equation, while nonpolar contributions are treated with a surface area-dependent term proportional to a surface tension coefficient, γ. To apply the FDPB/γ method to nonaqueous phases, it is necessary to derive a continuum representation of solute−solvent interactions appropriate for such systems. It is argued in this work that solute cavities in nonpolar solvents are significantly larger than in aqueous media. The physical basis for the existence of an expanded cavity in nonpolar solvents is discussed. When an expanded cavity, described in terms of increased values for atomic radii, is incorporated into the FDPB/γ formalism, good agreement between calculated and experimental solvation free energies is obtained. A new PARSE parameter set is developed for the transfer of organic molecules between alkanes and water which yields an average absolute error in solvation free energies of 0.2 kcal/mol for the 18 small molecules for which the parameters were optimized.

Chemical space sampling by different scoring functions and crystal structures

“…Multi-tiered docking and scoring workflows are especially attractive as a much more limited number of ligands and poses can be considered after an initial screen, and thus more rigorous and timeconsuming scoring functions can be applied. The MM-PBSA [46,47] or MM-GBSA scoring functions [48] are of particular interest in this work, which combine gas phase molecular mechanics interaction terms with polar desolvation energies from the Poisson-Boltzmann (PB) [49,50] or Generalized Born (GB) [48] equation, and a solvent-accessible surface area term [51,52] to account for nonpolar desolvation effects upon complex formation. Several recent papers have highlighted the utility of MM-PBSA or MM-GBSA in both pose prediction [42,43], virtual screening enrichment [42], and in correlation with experimental binding free energies [53,54].…”

Two SCA (Stigma/Style Cysteine-rich Adhesin) Isoforms Show Structural Differences That Correlate with Their Levels of in Vitro Pollen Tube Adhesion Activity

“…The conserved N-terminal Tyr 17 (in maize LTP numbering) on the helix H1 is mostly solvent-exposed (12), and its role in the lipid complexation is obscure. In the conserved Asp-Arg sequence of maize LTP, three arginine residues (Arg 41 , Arg 46 , and Arg 47 ) interact with an anionic phosphate group, and an aspartic acid (Asp 45 ) is located in the vicinity of the positive choline moiety of the palmitoyllysophosphatidylcholine (12).…”

Modelos contínuos do solvente: fundamentos

“…O teorema de Gauss estabelece que, em uma superfície fechada, a integral de superfície do campo elétrico é igual à carga total Q dentro da superfície dividido por ε o , como na Equação abaixo: (18) Desde que a carga total é dada pela integral da densidade de carga externa (ρ) e de densidade de carga de polarização (σ v ), teremos: (19) que pode ser escrito como: (20) Rearranjando, obtêm-se: (21) O vetor entre parênteses na primeira integral é denominado deslocamento elétrico ( D), e definimos a permissividade ε do meio como: (22) de forma que: (23) e a Equação 21 pode ser reescrita da forma: (24) Podemos agora usar o teorema da divergência para transformar a integral de superfície acima em uma integral de volume. A Equação resultante é: (25) Por fim, podemos fazer o volume acima se tornar tão pequeno, de forma que os integrandos sejam praticamente constantes no reduzido volume de integração. Nesta situação limite, a Equação 25 pode ser escrita na forma de uma Equação diferencial: (26) Usando a Equação 23, e o fato de que o vetor E é igual ao negativo do gradiente do potencial eletrostático total: (27) chegamos a: (28) Esta expressão é conhecida como Equação de Poisson 63 , e vale tanto dentro do dielétrico como no vácuo.…”