Insight into the structural requirements of antimicrobial peptides by multiple validated 3D-QSAR approaches

Antibacterial peptides (AMPs) are a kind of peptide material produced by the organism to resist the invasion of exogenous pathogens. Several antimicrobial peptides in different structures have been reported. To elucidate the relationship between structure and activity. A molecular modelling study on the nonapeptides using three-dimensional quantitative structure–activity relationship (3D-QSAR) was carried out. Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) methods were employed for the identification of significant features of antimicrobial peptides. CoMFA and CoMSIA models all gave best parametric results (Rcv2 = 0.563, Rpred2 = 0.654 for CoMFA; Rcv2 = 0.656, Rpred2 = 0.8045 for CoMSIA), which suggested that the derived models are highly robust and predictive. In addition, the derived contour maps would provide structural features to improve binding activity, and indicated that steric, electrostatic, and hydrophobic fields play vital roles in improving the activity. The derived models and information may help to provide an insight into the structural requirements for more potent peptides and facilitate the design and optimisation of novel antimicrobial peptides with promising enhanced activity. Furthermore, some potential candidate antimicrobial peptides have been proposed.