COMTOP: Protein Residue-Residue Contact Prediction through Mixed Integer Linear Optimization.

Md Selim Reza,Langxi Jin,Huiling Zhang,Shengzhong Feng,Md Tofazzal Hossain,Yanjie Wei

doi:10.3390/membranes11070503

Md Selim Reza, Langxi Jin + Show 4 more

Open Access

https://doi.org/10.3390/membranes11070503

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Abstract

Protein contact prediction helps reconstruct the tertiary structure that greatly determines a protein’s function; therefore, contact prediction from the sequence is an important problem. Recently there has been exciting progress on this problem, but many of the existing methods are still low quality of prediction accuracy. In this paper, we present a new mixed integer linear programming (MILP)-based consensus method: a Consensus scheme based On a Mixed integer linear opTimization method for prOtein contact Prediction (COMTOP). The MILP-based consensus method combines the strengths of seven selected protein contact prediction methods, including CCMpred, EVfold, DeepCov, NNcon, PconsC4, plmDCA, and PSICOV, by optimizing the number of correctly predicted contacts and achieving a better prediction accuracy. The proposed hybrid protein residue–residue contact prediction scheme was tested in four independent test sets. For 239 highly non-redundant proteins, the method showed a prediction accuracy of 59.68%, 70.79%, 78.86%, 89.04%, 94.51%, and 97.35% for top-5L, top-3L, top-2L, top-L, top-L/2, and top-L/5 contacts, respectively. When tested on the CASP13 and CASP14 test sets, the proposed method obtained accuracies of 75.91% and 77.49% for top-L/5 predictions, respectively. COMTOP was further tested on 57 non-redundant α-helical transmembrane proteins and achieved prediction accuracies of 64.34% and 73.91% for top-L/2 and top-L/5 predictions, respectively. For all test datasets, the improvement of COMTOP in accuracy over the seven individual methods increased with the increasing number of predicted contacts. For example, COMTOP performed much better for large number of contact predictions (such as top-5L and top-3L) than for small number of contact predictions such as top-L/2 and top-L/5. The results and analysis demonstrate that COMTOP can significantly improve the performance of the individual methods; therefore, COMTOP is more robust against different types of test sets. COMTOP also showed better/comparable predictions when compared with the state-of-the-art predictors.

Highlights

This article is an open access articleProtein contact prediction aims at predicting which residues of a protein are in contact.Two non-local residues are far away from each other in the protein primary structure, but they are close to each other in the 3D structure
When tested on CASP13, CASP14, and 57 non-redundant TM proteins, the consensus method achieved accuracies of 75.91%, 77.49%, and 73.91% for top-L/5 predictions, which was better than the seven individual methods and could achieve state-of-the-art prediction performance
We presented a novel hybrid consensus method named as COMTOP

Summary

Introduction

Protein contact prediction aims at predicting which residues of a protein are in contact. Two non-local residues are far away from each other in the protein primary structure, but they are close to each other in the 3D structure. A protein contact map is a 2D representation of a protein’s 3D structure. Contact map information can be used as distance restraints to guide protein structure modeling [4,5,6,7,8,9,10]. This creates a new direction for solving the grand challenge of the de novo protein structure. The idea of residue–residue contact prediction and using it to predict 3D models was introduced around two decades ago [11,12]; the realization of that idea has only recently gained much attention by the community and has come into practice as many authors have shown how residue contacts can be predicted with reasonable accuracy [13,14,15,16,17,18,19,20]

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