Small-size peptides acting as inhibitors of the BACE1-exosite. A molecular modeling study using MD simulations, QM calculations and QTAIM analysis.

GUTIERREZ, LUCAS; ANGELINA, EMILIO; PERUCHENA, NÉLIDA; BALDONI, HECTOR; ENRIZ, RICARDO DANIEL

Santiago

Congreso; 10th Congress of the World Association of Theoretical and Computational Chemists (WATOC 2014); 2014

Pontificia Universidad Católica de Chile

In this work a molecular modeling study on small-size peptides possessing inhibitory effect against BACE1 was carried out. By combining Molecular Dynamics (MD) simulations with ab initio and Density Functional Theory (DFT) calculations, a simple and generally applicable procedure to evaluate the binding energies of small-size peptides interacting with the BACE1-exosite binding site is reported here. Additionally, we report the results obtained by charge density analysis of the network of non covalent interactions in the exosite of BACE1, by formation of complexes with small-size peptides acting as inhibitors. These interactions have been investigated within the framework of the DFT and the Quantum Theory of Atoms in Molecules (QTAIM) using a reduced model. Although the approach used here was traditionally applied to the study of non covalent interactions in small molecules complexes in gas phase, we show through this work that this methodology is also a very powerful tool for the study of biomolecular complexes, providing a very detailed description of the binding event of peptides inhibitors at the exosite of BACE1.