Dataset Information

Identification of Intrinsically Disordered Proteins and Regions by Length-Dependent Predictors Based on Conditional Random Fields.

ABSTRACT: Accurate identification of intrinsically disordered proteins/regions (IDPs/IDRs) is critical for predicting protein structure and function. Previous studies have shown that IDRs of different lengths have different characteristics, and several classification-based predictors have been proposed for predicting different types of IDRs. Compared with these classification-based predictors, the previously proposed predictor IDP-CRF exhibits state-of-the-art performance for predicting IDPs/IDRs, which is a sequence labeling model based on conditional random fields (CRFs). Motivated by these methods, we propose a predictor called IDP-FSP, which is an ensemble of three CRF-based predictors called IDP-FSP-L, IDP-FSP-S, and IDP-FSP-G. These three predictors are specially designed to predict long, short, and generic disordered regions, respectively, and they are constructed based on different features. To the best of our knowledge, IDP-FSP is the first predictor that combines a sequence labeling algorithm with IDRs of different lengths. Experimental results using two independent test datasets show that IDP-FSP achieves better or at least comparable predictive performance with 26 existing state-of-the-art methods in this field, proving the effectiveness of IDP-FSP.

SUBMITTER: Liu Y

PROVIDER: S-EPMC6626971 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:The focus of the computational structural biology community has taken a dramatic shift over the past one-and-a-half decades from the classical protein structure prediction problem to the possible understanding of intrinsically disordered proteins (IDP) or proteins containing regions of disorder (IDPR). The current interest lies in the unraveling of a disorder-to-order transitioning code embedded in the amino acid sequences of IDPs/IDPRs. Disordered proteins are characterized by an enormous amount of structural plasticity which makes them promiscuous in binding to different partners, multi-functional in cellular activity and atypical in folding energy landscapes resembling partially folded molten globules. Also, their involvement in several deadly human diseases (e.g. cancer, cardiovascular and neurodegenerative diseases) makes them attractive drug targets, and important for a biochemical understanding of the disease(s). The study of the structural ensemble of IDPs is rather difficult, in particular for transient interactions. When bound to a structured partner, an IDPR adapts an ordered conformation in the complex. The residues that undergo this disorder-to-order transition are called protean residues, generally found in short contiguous stretches and the first step in understanding the modus operandi of an IDP/IDPR would be to predict these residues. There are a few available methods which predict these protean segments from their amino acid sequences; however, their performance reported in the literature leaves clear room for improvement. With this background, the current study presents 'Proteus', a random forest classifier that predicts the likelihood of a residue undergoing a disorder-to-order transition upon binding to a potential partner protein. The prediction is based on features that can be calculated using the amino acid sequence alone. Proteus compares favorably with existing methods predicting twice as many true positives as the second best method (55 vs. 27%) with a much higher precision on an independent data set. The current study also sheds some light on a possible 'disorder-to-order' transitioning consensus, untangled, yet embedded in the amino acid sequence of IDPs. Some guidelines have also been suggested for proceeding with a real-life structural modeling involving an IDPR using Proteus.

Dataset Information

Identification of Intrinsically Disordered Proteins and Regions by Length-Dependent Predictors Based on Conditional Random Fields.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets