The importance of physicochemical characteristics and nonlinear classifiers in determining HIV-1 protease specificity

ABSTRACT

This paper reviews recent research relating to the application of bioinformatics approaches to determining HIV-1 protease specificity, outlines outstanding issues, and presents a new approach to addressing these issues. Leading machine learning theory for the problem currently suggests that the direct encoding of the physicochemical properties of the amino acid substrates is not required for optimal performance. A number of amino acid encoding approaches which incorporate potentially relevant physicochemical properties of the substrate are identified, and are evaluated using a nonlinear task decomposition based neuroevolution algorithm. The results are evaluated, and compared against a recent benchmark set on a nonlinear classifier using only amino acid sequence and identity information. Ensembles of these nonlinear classifiers using the physicochemical properties of the substrate are demonstrated to consistently outperform the recently published state-of-the-art linear support vector machine based approach in out-of-sample evaluations.

KEYWORDS:

• amino acid encoding
• HIV-1
• neural networks
• physicochemical
• protease specificity
• SVM

Disclosure of potential conflicts of interest

No potential conflicts of interest were disclosed.

Funding

This work was funded by the European Commission, Horizon 2020 Marie Skłodowska-Curie Research and Innovation Staff Exchange, under grant no 644186 to P.W. and a Cork Institute of Technology Rísam Scholarship to T.M.