Subsets of Slow Dynamic Modes Reveal Global Information Sources as Allosteric Sites |
| |
Institution: | 1. Department of Chemical Engineering, Bogazici University, 34342 Istanbul, Turkey;2. Polymer Research Center, Bogazici University, 34342 Istanbul, Turkey;3. Department of Chemical and Biological Engineering, Koc University, 34450 Istanbul, Turkey |
| |
Abstract: | Allostery is a key biological control mechanism, and dynamic information flow provides a perspective to describe allosteric interactions in causal relationships. Here, as a novel implementation of the Gaussian Network Model (GNM) based Transfer Entropy (TE) calculations, we show that the dissection of dynamic information into subsets of slow dynamic modes discloses different layers of multi-directional allosteric pathways inherent in a given protein structure. In these subsets of slow modes, the degree of collectivity (Col) in the information transfer of residues with their TE values (TECol score) identifies distinct residues as powerful effectors, global information sources; showing themselves with a high dynamic capacity to collectively disseminate information to others. As exemplified on aspartate transcarbamoylase (ATCase), Na+/K+-adenosine triphosphatase (Na+/K+-ATPase), and human transient receptor potential melastatin 2 (TRPM2) along with a dataset of 20 proteins, these specific residues are associated with known active and allosteric sites. These information source residues, which collectively control others and lead allosteric communication pathways, hint at plausible binding sites for structure-based rational drug design. |
| |
Keywords: | allostery information transfer causality collectivity global information sources GNM"} {"#name":"keyword" "$":{"id":"pc_IorA6XYqW7"} "$$":[{"#name":"text" "_":"Gaussian Network Model TE"} {"#name":"keyword" "$":{"id":"pc_EtCkxSAcjt"} "$$":[{"#name":"text" "_":"Transfer Entropy TECol"} {"#name":"keyword" "$":{"id":"pc_BMciIVVPkC"} "$$":[{"#name":"text" "_":"Score of collective information transfer Col"} {"#name":"keyword" "$":{"id":"pc_AseSVUEzj7"} "$$":[{"#name":"text" "_":"Collectivity in information transfer |
本文献已被 ScienceDirect 等数据库收录! |
|