Exploring and Engineering the Conformational Landscape of Calmodulin through Specific Interactions
| Autor: | Ritaban Halder, Biman Jana |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Work (thermodynamics)
Calmodulin Protein Conformation Glycine Glutamic Acid Molecular Dynamics Simulation 010402 general chemistry 01 natural sciences Closed state Molecular dynamics Protein Domains 0103 physical sciences Materials Chemistry Physical and Theoretical Chemistry Stable state 010304 chemical physics biology Chemistry Lysine State (functional analysis) Salt bridge (protein and supramolecular) 0104 chemical sciences Surfaces Coatings and Films Mutation Biophysics biology.protein |
| Zdroj: | The Journal of Physical Chemistry B. 123:9321-9327 |
| ISSN: | 1520-5207 1520-6106 |
| DOI: | 10.1021/acs.jpcb.9b06343 |
| Popis: | Conformational fluctuations often play paramount role in the function and activity of proteins. Calmodulin (CaM) is a calcium sensing protein that shows significant conformational flexibility on going from a ligand-free open state to a ligand-bound closed state. By employing large-scale equilibrium molecular dynamics simulations and free energy calculations, we have shown that apo CaM frequently visits a state that is neither fully open nor fully closed and referred to as half-open half-closed (HOHC) state. Such states are functionally relevant as they structurally resemble a ligand-bound closed state. Here, we have envisaged that the inherent conformational dynamics of CaM is primarily triggered by a dual salt bridge interaction between the glutamates and lysine at two different domains (N- and C-terminal domains) of the protein. Upon abolition of the dual salt bridge interaction, conformational dynamics is restricted and centered only near the open state. When a cation-π interaction is introduced while replacing the dual salt bridge interaction, the HOHC state tends to reappear as a stable state. Since salt bridge and cation-π interactions are frequently encountered in the protein dynasty, our work may illuminate an interesting direction toward controlling the conformational landscape of proteins through the modulation of minimal specific interactions. |
| Databáze: | OpenAIRE |
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