Insight into molecular interactions of Aβ peptide and gelatinase from Enterococcus faecalis: a molecular modeling approach

Alzheimer's disease is characterized by the presence of extracellular deposition of amyloid beta (A beta) peptides. The A beta levels are maintained by a suitable balance between its production and clearance via receptor-mediated cellular uptake and direct enzymatic degradation. However, decreased production of A beta degrading enzymes and loss of A beta degrading activity in the human brain initiates the process of accumulation of A beta peptides. Mutations in amyloid beta peptides are also known to reduce clearance of A beta peptides. So it becomes necessary to understand molecular interactions involved in the process of A beta degradation in detail at the atomic level. Hence, in this study, we used molecular docking and molecular dynamics simulation techniques to explore molecular interactions between gelatinase from Enterococcus faecalis and A beta peptide. The comparison between wild type and mutant A beta peptides revealed that the docked complex of gelatinase-wild type A beta peptide is more stable as compared to mutant complex. These results showed that the residue Glu 328 of gelatinase from E. faecalis might play a catalytic role by serving as a proton shuttle to cleave wild type A beta peptide in between Leu 34-Met 35. Thus, the results obtained from this study might be useful to design new strategies against A beta peptide degradation.