Evaluation of the Effectiveness of Derived Features of AlphaFold2 on Single-Sequence Protein Binding Site Prediction.

Abstract

Simple SummaryWith the development of artificial intelligence, researchers can roughly predict the crystal structure of a protein by computer without the need for biological experiments, which provides new ideas and solutions to problems, such as protein-protein interaction and drug-target predictions. In this study, we proposed strategies to combine predicted protein structures with deep learning networks and evaluated them on different protein binding site prediction tasks. Our computational experiment results showed that all proposed strategies could effectively encode structural information for deep learning models.Though AlphaFold2 has attained considerably high precision on protein structure prediction, it is reported that directly inputting coordinates into deep learning networks cannot achieve desirable results on downstream tasks. Thus, how to process and encode the predicted results into effective forms that deep learning models can understand to improve the performance of downstream tasks is worth exploring. In this study, we tested the effects of five processing strategies of coordinates on two single-sequence protein binding site prediction tasks. These five strategies are spatial filtering, the singular value decomposition of a distance map, calculating the secondary structure feature, and the relative accessible surface area feature of proteins. The computational experiment results showed that all strategies were suitable and effective methods to encode structural information for deep learning models. In addition, by performing a case study of a mutated protein, we showed that the spatial filtering strategy could introduce structural changes into HHblits profiles and deep learning networks when protein mutation happens. In sum, this work provides new insight into the downstream tasks of protein-molecule interaction prediction, such as predicting the binding residues of proteins and estimating the effects of mutations.