Abstract

An in silico screening method for novel dipeptides from a dipeptide training set was performed. A 3D pharmacophore model with three H-bond acceptor projections (Acc2), and one H-bond donor projection (Don2) was obtained. To validate the pharmacophore model, a test set containing 10 reported dipeptides was screened and all were found to be bioactive. Eleven novel dipeptides (IF, GD, DA, TE, TA, ES, SS, ST, SD, QD, QE) from the silkworm pupae protein peptide database were predicted to have ACE inhibitory bioactivity. The interaction mechanisms of the dipeptides with the ACE active pocket were elucidated by molecule docking, and besides involving interaction bonds, the interaction force equipoise of the peptides was also an important factor in their bioactivity.

Keywords: Angiotensin-I-converting enzyme, in silico, molecular mechanism, screening, silkworm pupae.