Mapping allosteric communications within individual proteins

• Published in: Nature communications Vol. 11; no. 1; pp. 3862 - 13
• Main Authors: Wang, Jian, Jain, Abha, McDonald, Leanna R, Gambogi, Craig, Lee, Andrew L, Dokholyan, Nikolay V
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 31.07.2020; Nature Publishing Group UK; Nature Portfolio
• Subjects: Algorithms; Allosteric properties; Allosteric Regulation; Allosteric Site; Animals; Biological activity; Communication networks; Computer applications; Computer architecture; Computer networks; Computer simulation; Correlation analysis; Coupling; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacology; Escherichia coli - enzymology; Escherichia coli - genetics; Escherichia coli Proteins; Gene regulation; Humans; Internet; Methyl-Accepting Chemotaxis Proteins - antagonists & inhibitors; Methyl-Accepting Chemotaxis Proteins - chemistry; Methyl-Accepting Chemotaxis Proteins - metabolism; Molecular Dynamics Simulation; Mutation; NMR; Nuclear magnetic resonance; Peptide mapping; Predictions; Protein Interaction Mapping - statistics & numerical data; Protein structure; Protein Structure, Secondary; Proteins; Software; Transcription
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-020-17618-2

Allostery in proteins influences various biological processes such as regulation of gene transcription and activities of enzymes and cell signaling. Computational approaches for analysis of allosteric coupling provide inexpensive opportunities to predict mutations and to design small-molecule agents to control protein function and cellular activity. We develop a computationally efficient network-based method, Ohm, to identify and characterize allosteric communication networks within proteins. Unlike previously developed simulation-based approaches, Ohm relies solely on the structure of the protein of interest. We use Ohm to map allosteric networks in a dataset composed of 20 proteins experimentally identified to be allosterically regulated. Further, the Ohm allostery prediction for the protein CheY correlates well with NMR CHESCA studies. Our webserver, Ohm.dokhlab.org, automatically determines allosteric network architecture and identifies critical coupled residues within this network.