CoMemMoRFPred: Sequence-based Prediction of MemMoRFs by Combining Predictors of Intrinsic Disorder, MoRFs and Disordered Lipid-binding Regions

Molecular recognition features (MoRFs) are a commonly occurring type of intrinsically disordered regions (IDRs) that undergo disorder-to-order transition upon binding to partner molecules. We focus on recently characterized and functionally important membrane-binding MoRFs (MemMoRFs). Motivated by the lack of computational tools that predict MemMoRFs, we use a dataset of experimentally annotated Mem-MoRFs to conceptualize, design, evaluate and release an accurate sequence-based predictor. We rely on state-of-the-art tools that predict residues that possess key characteristics of MemMoRFs, such as intrinsic disorder, disorder-to-order transition and lipid-binding. We identify and combine results from three tools that include flDPnn for the disorder prediction, DisoLipPred for the prediction of disordered lipid-binding regions, and MoRFCHiBiLight for the prediction of disorder-to-order transitioning protein binding regions. Our empirical analysis demonstrates that combining results produced by these three methods generates accurate predictions of MemMoRFs. We also show that use of a smoothing operator produces predictions that closely mimic the number and sizes of the native MemMoRF regions. The resulting CoMemMoRFPred method is available as an easy-to-use webserver at http://biomine.cs.vcu.edu/ser-vers/CoMemMoRFPred. This tool will aid future studies of MemMoRFs in the context of exploring their abundance, cellular functions, and roles in pathologic phenomena. (c) 2023 Elsevier Ltd. All rights reserved.

Automated summary

In this study, we propose an accurate sequence-based predictor for membrane-binding MoRFs and demonstrate its effectiveness. The tool will contribute to future studies on the abundance, cellular functions, and roles of MemMoRFs in pathological phenomena.