In silico rational design and virtual screening of antixoidant tripeptides based on 3D-QSAR modeling

Abstract

Antioxidant peptides play an important role in preventing the harmful effects of free radicals against human tissues, by inhibiting and delaying lipid oxidation. Plenty of peptides have been reported by recent literature. Tripeptides, one of the interesting antioxidants, have shown good antioxidant activity. Here, we collected 198 antioxidant tripeptides from literature and applied comparative molecular field analysis (CoMFA) and comparative similarity index analysis (CoMSIA) to construct three-dimension quantitative structure-activity relationship (3D-QSAR) models, which were used to guide combinations design and virtual screening for novel peptides. The CoMFA and CoMISA models had good predictability (R2: 0.735 vs 0.733) and stability (Q2: 0.885 vs 0.914). The contour maps indicated steric, electrostatic, hydrophilic and hydrogen bond acceptor force fields contributed greatly to the antioxidant activity, which could give directly and graphical information for rational design and modification of novel peptides. Consequently, we designed and synthesized 10 new tripeptides and tested their relative antioxidant activity by FRAP and ABTA methods. As a result, most of them showed good antioxidant effects. The high correlation between observed and predicted activity indicated a good predictability of our 3D-QSAR models, which could be used for the combinational design and virtual screening of antioxidant peptides.