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Nonequilibrium Modeling of the Elementary Step in PDZ3 Allosteric Communication
- Source :
- The Journal of Physical Chemistry Letters 13.42 (2022): 9862-9868
- Publication Year :
- 2022
-
Abstract
- While allostery is of paramount importance for protein signaling and regulation, the underlying dynamical process of allosteric communication is not well understood. PDZ3 domain represents a prime example of an allosteric single-domain protein, as it features a well-established long-range coupling between the C-terminal $\alpha_3$-helix and ligand binding. In an intriguing experiment, Hamm and coworkers employed photoswitching of the $\alpha_3$-helix to initiate a conformational change of PDZ3 that propagates from the C-terminus to the bound ligand within 200 ns. Performing extensive nonequilibrium molecular dynamics simulations, the modeling of the experiment reproduces the measured timescales and reveals a detailed picture of the allosteric communication in PDZ3. In particular, a correlation analysis identifies a network of contacts connecting the $\alpha_3$-helix and the core of the protein, which move in a concerted manner. Representing a one-step process and involving direct $\alpha_3$-ligand contacts, this cooperative transition is considered as elementary step in the propagation of conformational change.
- Subjects :
- Physics - Biological Physics
Quantitative Biology - Biomolecules
Subjects
Details
- Database :
- arXiv
- Journal :
- The Journal of Physical Chemistry Letters 13.42 (2022): 9862-9868
- Publication Type :
- Report
- Accession number :
- edsarx.2209.07829
- Document Type :
- Working Paper
- Full Text :
- https://doi.org/10.1021/acs.jpclett.2c02821