BION-2: Predicting Positions of Non-Specifically Bound Ions on Protein Surface by a Gaussian-Based Treatment of Electrostatics.

H B Mihiri Shashikala,Shailesh Kumar Panday,Emil Alexov,Arghya Chakravorty

doi:10.3390/ijms22010272

H B Mihiri Shashikala, Shailesh Kumar Panday + Show 2 more

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https://doi.org/10.3390/ijms22010272

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Abstract

Ions play significant roles in biological processes—they may specifically bind to a protein site or bind non-specifically on its surface. Although the role of specifically bound ions ranges from actively providing structural compactness via coordination of charge–charge interactions to numerous enzymatic activities, non-specifically surface-bound ions are also crucial to maintaining a protein’s stability, responding to pH and ion concentration changes, and contributing to other biological processes. However, the experimental determination of the positions of non-specifically bound ions is not trivial, since they may have a low residential time and experience significant thermal fluctuation of their positions. Here, we report a new release of a computational method, the BION-2 method, that predicts the positions of non-specifically surface-bound ions. The BION-2 utilizes the Gaussian-based treatment of ions within the framework of the modified Poisson–Boltzmann equation, which does not require a sharp boundary between the protein and water phase. Thus, the predictions are done by the balance of the energy of interaction between the protein charges and the corresponding ions and the de-solvation penalty of the ions as they approach the protein. The BION-2 is tested against experimentally determined ion’s positions and it is demonstrated that it outperforms the old BION and other available tools.

Highlights

Ions are an important component of biological systems as they interact with macromolecules and directly participate in a wide range of reactions [1,2,3]
The ions can be broadly grouped into two categories: mobile ions in the water phase and ions bound to the corresponding macromolecule
This work focusses on such a type of ions and reports a new development of an algorithm, the BION-2 algorithm, that predicts the positions of non- surface-bound ions

Summary

Introduction

Ions are an important component of biological systems as they interact with macromolecules and directly participate in a wide range of reactions [1,2,3]. The ions can be broadly grouped into two categories: mobile ions in the water phase and ions bound to the corresponding macromolecule. The ions bound to macromolecules are involved in specific interactions with macromolecular moiety and play roles in catalysis, electron/proton transfer reactions, and structural stability [6,7,8]. In between these two well distinguishable categories are ions that are weakly bound to the macromolecular surface, without being involved in specific chemical interaction, and have a low residential time—the non- surface-bound ions [9]. This work focusses on such a type of ions and reports a new development of an algorithm, the BION-2 algorithm, that predicts the positions of non- surface-bound ions

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Results

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