ArticleProceedings of the National Academy of Sciences of the United States of America2017
Hidden electrostatic basis of dynamic allostery in a PDZ domain.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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39 citing papers in PubMed.
- Article
- Surface electrostatic networks control hydrophobic core remodeling in a pH-dependent switching protein.bioRxiv : the preprint server for biology · 2026Article
- Identification of Key Residues in Allosteric Signaling of Photoactivated Adenylyl Cyclase.bioRxiv : the preprint server for biology · 2026Article
- Allostery in Biomolecular Condensates.Journal of molecular biology · 2026Review
- Contact Cluster Modeling of Allosteric Communication in PDZ Domains.The journal of physical chemistry. B · 2026Review
- Natural Fatty Acids as Dual ACE2-Inflammatory Modulators: Integrated Computational Framework for Pandemic Preparedness.International journal of molecular sciences · 2025Article
- Functional Variation in RGS12 Should Not Preclude Methylphenidate Use in Bipolar Disorder with Established Mood Stabilization: Preclinical Evidence.International journal of molecular sciences · 2025Article
- ERK Allosteric Activation: The Importance of Two Ordered Phosphorylation Events.Journal of molecular biology · 2025Article
- Network Theory Analysis of Allosteric Drug-Rescue Mechanisms in the Tumor Suppressor Protein p53 Y220C Mutant.International journal of molecular sciences · 2025Article
- Application of Anomaly Detection to Identify Important Features of Protein Dynamics.ACS omega · 2025Article
- Synaptic Physiology Depends on Electrical Forces and Liquid-Liquid Phase Separation.Reviews of physiology, biochemistry and pharmacology · 2025Review
- Molecular mechanism of regulation of RhoA GTPase by phosphorylation of RhoGDI.Biophysical journal · 2024Article
- Allosteric Signaling in PDZ Energetic Networks: Embedding Error Analysis.The journal of physical chemistry. B · 2023Article
- Investigating the allosteric response of the PICK1 PDZ domain to different ligands with all-atom simulations.Protein science : a publication of the Protein Society · 2022Article
- Article
- Resonance assignment of the Shank1 PDZ domain.Biomolecular NMR assignments · 2022Article
- Allosterism in the PDZ Family.International journal of molecular sciences · 2022Review
- Hidden electrostatic energy contributions define dynamic allosteric communications within p53 during molecular recognition.Biophysical journal · 2021Article
- Dynamic energy correlation analysis ofEngineering in life sciences · 2021Article
- Ensemble-Based Analysis of the Dynamic Allostery in the PSD-95 PDZ3 Domain in Relation to the General Variability of PDZ Structures.International journal of molecular sciences · 2020Article
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2 authors.
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No grant is acknowledged in the PubMed record.
Abstract
Allosteric effect implies ligand binding at one site leading to structural and/or dynamical changes at a distant site. PDZ domains are classic examples of dynamic allostery without conformational changes, where distal side-chain dynamics is modulated on ligand binding and the origin has been attributed to entropic effects. In this work, we unearth the energetic basis of the observed dynamic allostery in a PDZ3 domain protein using molecular dynamics simulations. We demonstrate that electrostatic interaction provides a highly sensitive yardstick to probe the allosteric modulation in contrast to the traditionally used structure-based parameters. There is a significant population shift in the hydrogen-bonded network and salt bridges involving side chains on ligand binding. The ligand creates a local energetic perturbation that propagates in the form of dominolike changes in interresidue interaction pattern. There are significant changes in the nature of specific interactions (nonpolar/polar) between interresidue contacts and accompanied side-chain reorientations that drive the major redistribution of energy. Interestingly, this internal redistribution and rewiring of side-chain interactions led to large cancellations resulting in small change in the overall enthalpy of the protein, thus making it difficult to detect experimentally. In contrast to the prevailing focus on the entropic or dynamic effects, we show that the internal redistribution and population shift in specific electrostatic interactions drive the allosteric modulation in the PDZ3 domain protein.
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