Solvent accessible surface area approximations for rapid and accurate protein structure prediction

The burial of hydrophobic amino acids in the protein core is a driving force in protein folding. The extent to which an amino acid interacts with the solvent and the protein core is naturally proportional to the surface area exposed to these environments. However, an accurate calculation of the solvent-accessible surface area (SASA), a geometric measure of this exposure, is numerically demanding as it is not pair-wise decomposable. Furthermore, it depends on a full-atom representation of the molecule. This manuscript introduces a series of four SASA approximations of increasing computational complexity and accuracy as well as knowledge-based environment free energy potentials based on these SASA approximations. Their ability to distinguish correctly from incorrectly folded protein models is assessed to balance speed and accuracy for protein structure prediction. We find the newly developed “Neighbor Vector” algorithm provides the most optimal balance of accurate yet rapid exposure measures

DYNAMIC SURFACE BOUNDARY-CONDITIONS - A SIMPLE BOUNDARY MODEL FOR MOLECULAR-DYNAMICS SIMULATIONS

A simple model for the treatment of boundaries in molecular dynamics simulations is presented. The method involves the positioning of boundary atoms on a surface that surrounds a system of interest. The boundary atoms interact with the inner region and represent the effect of atoms outside the surface on the dynamics of the atoms inside the surface. The boundary atoms can move but are position restrained. A simple application to liquid argon in a sphere is demonstrated. The methodologies are illustrated for calculating the radial distribution function, density, pressure, potential energy per atom and chemical potential. Also the velocity autocorrelation function and the diffusion constant are calculated. To derive the parameters of the model an empirical approach was followed which consisted of comparing the simulation results of the boundary model with simulation results using periodic boundary conditions. The conclusion is that the present method is able to reproduce the dynamical, structural and thermodynamical properties of a Lennard-Jones liquid. The applicability to systems with long-ranged forces is discussed

SUCCESS AND PITFALLS OF THE DIELECTRIC CONTINUUM MODEL IN QUANTUM-CHEMICAL CALCULATIONS

Recently we presented an extension of the direct reaction field (DRF) method, in which a quantum system and a set of point charges and interacting polarizabilities are embedded in a continuum that is characterized by a dielectric constant epsilon and a finite ionic strength. The reaction field of the continuum is found by solving the (linearized) Poisson-Boltzmann equation by a boundary element method for the complete charge distribution in a cavity of arbitrary size and form. Like many other authors, we found that the results depend critically on the choice of the size of the cavity, in the sense that the continuum contribution to the solvation energy decreases rapidly with the relative cavity size. The literature gives no clues for the definition of the cavity size beyond ''physical intuition'' or implicit fitting to experimental or otherwise desired results. From theoretical considerations, a number of limitations on the position of the boundary are derived. With a boundary defined within these limitations, the experimental hydration energies cannot be reproduced, mainly because of the neglected specific interactions. In addition, we found that the description of the solute's electronic states also depends on the solvation model. We suggest that one or more explicit solvent layers are needed to obtain reliable solvation and excitation energies. (C) 1993 John Wiley & Sons, Inc

QUANTUM-CHEMISTRY IN THE CONDENSED PHASE - AN EXTENDED DIRECT REACTION FIELD APPROACH

The direct reaction field (DRF) approach is a practical method for incorporating environmental (e.g. solvation) effects on a system of which the electronic charge distribution is described by wave functions, and the "solvent" is modelled by a collection of interacting point charges and (point) polarizabilities. The DRF method is briefly summarized. Next, we present a numerical solution-based on a boundary element method-of the Poisson (-Boltzmann) equation for a set of quantum mechanical and/or point charges in a cavity in a dielectric continuum which may have a finite ionic strength. Finally, we describe the solution of these equations for the situation in which the cavity contains a set of charges and polarizabilities