2 research outputs found

    PREvaIL, an integrative approach for inferring catalytic residues using sequence, structural and network features in a machine learning framework

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    Determining the catalytic residues in an enzyme is critical to our understanding the relationship between protein sequence, structure, function, and enhancing our ability to design novel enzymes and their inhibitors. Although many enzymes have been sequenced, and their primary and tertiary structures determined, experimental methods for enzyme functional characterization lag behind. Because experimental methods used for identifying catalytic residues are resource- and labor-intensive, computational approaches have considerable value and are highly desirable for their ability to complement experimental studies in identifying catalytic residues and helping to bridge the sequence–structure–function gap. In this study, we describe a new computational method called PREvaIL for predicting enzyme catalytic residues. This method was developed by leveraging a comprehensive set of informative features extracted from multiple levels, including sequence, structure, and residue-contact network, in a random forest machine-learning framework. Extensive benchmarking experiments on eight different datasets based on 10-fold cross-validation and independent tests, as well as side-by-side performance comparisons with seven modern sequence- and structure-based methods, showed that PREvaIL achieved competitive predictive performance, with an area under the receiver operating characteristic curve and area under the precision-recall curve ranging from 0.896 to 0.973 and from 0.294 to 0.523, respectively. We demonstrated that this method was able to capture useful signals arising from different levels, leveraging such differential but useful types of features and allowing us to significantly improve the performance of catalytic residue prediction. We believe that this new method can be utilized as a valuable tool for both understanding the complex sequence–structure–function relationships of proteins and facilitating the characterization of novel enzymes lacking functional annotations

    Identifying antimicrobial peptides in genomes using machine learning

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    Legana Fingerhut used machine learning to improve predictions of antimicrobial peptides (AMPs) from protein sequences. Her associated framework was the first to specifically address the problem of identifying AMPs from whole-genome data. Her work leads to improved workflows for identifying novel AMPs which advances our understanding of the innate immune system
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