ELECTRONIC PARAMETERS OF CONFORMATIONAL STATES OF ABETA-AMYLOID PEPTIDE (25-35)

Abstract

The electronic characteristics of stable conformational states of beta-amyloid peptide (25-35) have been studied by molecular modeling methods. Beta-amyloid peptide (Aβ) is the main component of senile plaques found in the brains of patients with Alzheimer's disease. Aβ (25-35) fragment of a molecule with the amino acid sequence Gly-Ser-Asn-Lys-Gly-Ala-Ile-Ile-Gly-Leu-Met. It has been shown that the conformational features of a molecule are largely determined by its environment; therefore, the aim of this work was to study the differences in the conformations of amyloid beta-peptide (25-35) in vacuum and in a low-polarity medium using the methods of molecular mechanics and quantum chemical calculations. The studies were carried out in two stages: 1) the geometric and energy parameters of the low-energy conformational states of the indicated peptide were determined, 2) the electronic characteristics of the established low-energy conformations of these molecule were calculated. Calculations showed that the conformational behavior of this peptide can be described by a set of similar low-energy conformations with structure on the C-terminal sequence. It has also been shown that the low-energy structures of the amyloid beta-peptide (25-35) have the most favorable dispersion contacts and, therefore, it can be expected that they will become most preferable in a low-polarity environment, when electrostatic interactions do not play a significant role. Permissible changes in the dihedral angles of the amyloid beta-peptide (25-35) in the energetically preferred conformation and the stability of secondary structure elements were also investigated. The distribution of electron density and equipotential surfaces in the energetically preferred conformations of the beta-amyloid peptide were obtained and compared (25-35). Quantum chemical calculations showed that the largest negative charges in the peptide are concentrated precisely on the oxygen atoms of the carbonyl groups and the nitrogen atoms of the amino group. The distribution of electron density and equipotential surfaces in the energetically preferred conformations of the beta-amyloid peptide (25-35) were obtained and compared.