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

作者：Gutierrez Lucas J; Barrera Guisasola Exequiel E; Peruchena Nelida; Enriz Ricardo D^*

来源：Molecular Simulation, 2016, 42(3): 196-207.

DOI：10.1080/08927022.2015.1032276

• Alzheimer's disease
• amyloid-beta peptide
• ONIOM calculations
• QTAIM analysis

The molecular mechanism of recognition of amyloid-beta (A) peptide isoforms by bapineuzumab was studied using a quantum mechanics and molecular mechanics (QM/MM) method. In this work, geometric optimisations were performed using the ONIOM2 scheme (at B3LYP/6-31G(d) amber)EE level) on the paratope of bapineuzumab together with the different forms of A peptide (A(WT) and AN3(pE)). A comprehensive study of the interactions was also performed through Quantum Theory of Atoms in Molecules (QTAIM). This allowed us to obtain a deep understanding of how this antibody interacts with the amino acids of the A peptides. The description on the interactions between bapineuzumab and the different forms of A 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 for a deeper understanding about the scope and limitations of bapineuzumab as a therapeutic agent for the AD.

• 出版日期2016-2-11