There are many paths to solvation

Abstract

Two ab initio studies are presented herein. The first is of the addition of successive water molecules to the amino acid L-alanine in both the neutral and zwitterion forms. The main focus is on the number of water molecules needed to stabilize the zwitterion form, and how the solvent affects conformational preference. The solvent is modeled by ab initio, EFP (Effective Fragment Potential), and the isotropic dielectrics PCM (Polarizable Continuum Method) bulk solvation techniques. The EFP discrete solvation model uses a Monte Carlo algorithm to sample the configuration space to find the global minimum. The study is undertaken at the EFP2(General Effective Fragment Potential), RHF (Restricted Hartree-Fock), DFT (Density Functional Theory), and MP2 (Moller-Plesset) levels of theory with a 6-31++G(d,p) atomic basis set. A Second study is presented of substrates for a pentameric ligand gated ion-channel, or Cys-loop receptor, which mediate chemical signals across the cellular membrane. Blocking specific signaling receptors may induce death in agricultural pests such as nematodes. Many biological signaling proteins have inter-membrane domains that cause difficulty in obtaining an x-ray diffraction structure. Further, those that have been elucidated with x-ray diffraction studies are static structures that do not capture the structural dynamics. Since there is a known set of competitive binding molecules, an ab initio study of the competitive binding molecules was employed. From this study one may be able to design new competitive binding molecules that will mitigate resistance to current methods of pest control. The ab initio methods include Moller-Plesset second order perturbation theory with the 6-31G(d,p) basis set, adding diffuse functions when solvents are used. The solvent model employs a discrete ab initio and effective fragment part along with the polarizable continuum method. A thorough understanding of the geometries and electron densities of known substrates can lead to the design and synthesis of competitive inhibitors that could improve crop yields and animal health. Calculations have been performed with the GAMESS (General Atomic and Molecular Electronic Structure System) suite of programs.