AnkPlex: algorithmic structure for refinement of near-native ankyrin-protein docking

Tanchanok Wisitponchai,Watshara Shoombuatong,Kuntida Kitidee,Chatchai Tayapiwatana,Vannajan Sanghiran Lee

doi:10.1186/s12859-017-1628-6

Abstract

BackgroundComputational analysis of protein-protein interaction provided the crucial information to increase the binding affinity without a change in basic conformation. Several docking programs were used to predict the near-native poses of the protein-protein complex in 10 top-rankings. The universal criteria for discriminating the near-native pose are not available since there are several classes of recognition protein. Currently, the explicit criteria for identifying the near-native pose of ankyrin-protein complexes (APKs) have not been reported yet.ResultsIn this study, we established an ensemble computational model for discriminating the near-native docking pose of APKs named “AnkPlex”. A dataset of APKs was generated from seven X-ray APKs, which consisted of 3 internal domains, using the reliable docking tool ZDOCK. The dataset was composed of 669 and 44,334 near-native and non-near-native poses, respectively, and it was used to generate eleven informative features. Subsequently, a re-scoring rank was generated by AnkPlex using a combination of a decision tree algorithm and logistic regression. AnkPlex achieved superior efficiency with ≥1 near-native complexes in the 10 top-rankings for nine X-ray complexes compared to ZDOCK, which only obtained six X-ray complexes. In addition, feature analysis demonstrated that the van der Waals feature was the dominant near-native pose out of the potential ankyrin-protein docking poses.ConclusionThe AnkPlex model achieved a success at predicting near-native docking poses and led to the discovery of informative characteristics that could further improve our understanding of the ankyrin-protein complex. Our computational study could be useful for predicting the near-native poses of binding proteins and desired targets, especially for ankyrin-protein complexes. The AnkPlex web server is freely accessible at http://ankplex.ams.cmu.ac.th.

Highlights

Computational analysis of protein-protein interaction provided the crucial information to increase the binding affinity without a change in basic conformation
The results suggested that the ZDOCK calculation using pairwise shape complementarity (PSC) + DE + ELEC and the screening based on the recognition areas were the optimal calculations because this procedure was capable of incorporating near-native poses and eliminating non-near-native poses
The AnkPlex model was constructed based on a combination of features generated from the ZDOCK program without using manual inspections

Summary

Introduction

Computational analysis of protein-protein interaction provided the crucial information to increase the binding affinity without a change in basic conformation. Several docking programs were used to predict the near-native poses of the protein-protein complex in 10 top-rankings. The explicit criteria for identifying the near-native pose of ankyrin-protein complexes (APKs) have not been reported yet. Due to the complications involved in generating specific antibodies and their large size, alternative scaffolds have been developed to overcome these limitations. One of those novel scaffolds is comprised of Designed Ankyrin Repeat Proteins (DARPins). Modification of the residues at the variable part of ankyrin allows for increased binding affinity towards the target protein without changes in the basic protein conformation [9]. A computational approach, called protein–protein docking, can be used to generate protein complex structures because there were no available reports on the protein complex

Objectives

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Results

Conclusion