AVP-IC50 Pred: Multiple machine learning techniques-based prediction of peptide antiviral activity in terms of half maximal inhibitory concentration (IC50)

Abstract

Peptide-based antiviral therapeutics has gradually paved their way into mainstream drug discovery research. Experimental determination of peptides' antiviral activity as expressed by their IC50 values involves a lot of effort. Therefore, we have developed "AVP-IC50 Pred," a regression-based algorithm to predict the antiviral activity in terms of IC50 values (μM). A total of 759 non-redundant peptides from AVPdb and HIPdb were divided into a training/test set having 683 peptides (T(683)) and a validation set with 76 independent peptides (V(76)) for evaluation. We utilized important peptide sequence features like amino-acid compositions, binary profile of N8-C8 residues, physicochemical properties and their hybrids. Four different machine learning techniques (MLTs) namely Support vector machine, Random Forest, Instance-based classifier, and K-Star were employed. During 10-fold cross validation, we achieved maximum Pearson correlation coefficients (PCCs) of 0.66, 0.64, 0.56, 0.55, respectively, for the above MLTs using the best combination of feature sets. All the predictive models also performed well on the independent validation dataset and achieved maximum PCCs of 0.74, 0.68, 0.59, 0.57, respectively, on the best combination of feature sets. The AVP-IC50 Pred web server is anticipated to assist the researchers working on antiviral therapeutics by enabling them to computationally screen many compounds and focus experimental validation on the most promising set of peptides, thus reducing cost and time efforts. The server is available at http://crdd.osdd.net/servers/ic50avp.

Keywords: IC50; antiviral; machine learning; peptide; prediction.

Figure 1

Correlation between actual and predicted IC₅₀ values of the independent dataset using (a) SVM and (b) RF.

Figure 2

Two sample logo (TSL) comparison. TSLs Two sample logos of a) 8‐N terminal and b) 8‐C terminal residues of 97 highly effective peptides (IC₅₀ < 1 µM) and an equal number of least effective peptides (IC₅₀ > 100 µM).

Figure 3

AVP‐IC₅₀ Pred result output.