J Chem Inf Model. 2022 Jun 15. doi: 10.1021/acs.jcim.2c00526. Online ahead of print.
ABSTRACT
The discovery of therapeutic peptides is often accelerated by means of virtual screening supported by machine learning-based predictive models. The predictive performance of such models is sensitive to the choice of data and its representation scheme. While the peptide physicochemical and compositional representations fail to distinguish sequence permutations, the amino acid arrangement within the sequence lacks the important information contained in physicochemical, conformational, topological, and geometrical properties. In this paper, we propose a solution to the identified information gap by implementing a hybrid scheme that complements the best traits from both approaches with the aim of predicting antimicrobial and antiviral activities based on experimental data from DRAMP 2.0, AVPdb, and Uniprot data repositories. Using the Friedman test of statistical significance, we compared our hybrid, sequential properties approach to peptide properties, one-hot vector encoding, and word embedding schemes in the 10-fold cross-validation setting, with respect to the F1 score, Matthews correlation coefficient, geometric mean, recall, and precision evaluation metrics. Moreover, the sequence modeling neural network was employed to gain insight into the synergic effect of both properties- and amino acid order-based predictions. The results suggest that sequential properties significantly (P < 0.01) surpasses the aforementioned state-of-the-art representation schemes. This makes it a strong candidate for increasing the predictive power of screening methods based on machine learning, applicable to any category of peptides.
PMID:35704881 | DOI:10.1021/acs.jcim.2c00526
