A QM/MM study of the molecular recognition site of bapineuzumab toward the beta amyloid; peptide isoforms

L.GUTIERREZ; E.BARRERA; N.PERUCHENA; ENRIZ R.D.

MOLECULAR SIMULATION

TAYLOR & FRANCIS LTD

Lugar: Londres; Año: 2015

0892-7022

The molecular mechanism of recognition of amyloid-beta (Ab) peptide isoforms by bapineuzumab was studied using aquantum mechanics and molecular mechanics (QM/MM) method. In this work, geometric optimisations were performedusing the ONIOM2 scheme (at B3LYP/6-31G(d) amber)EE level) on the paratope of bapineuzumab together with thedifferent forms of Ab peptide (AbWT and AbN3(pE)). A comprehensive study of the interactions was also performedthrough Quantum Theory of Atoms in Molecules (QTAIM). This allowed us to obtain a deep understanding of how thisantibody interacts with the amino acids of the Ab peptides. The description on the interactions between bapineuzumab andthe different forms of Ab peptides allow us to understand why the peptides that lack the two first residues (Asp1 and Ala2)and begin with a pyroglutamate residue present low affinity for bapineuzumab. This basic structural information is useful fora deeper understanding about the scope and limitations of bapineuzumab as a therapeutic agent for the AD.