Molecular dynamics studies on conformational thermodynamics of Orai1–calmodulin complex
| Autor: | Jaydeb Chakrabarti, Mahua Ghosh, Lakshmi Maganti |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
animal structures Calmodulin ORAI1 Protein Protein Conformation Molecular Dynamics Simulation 03 medical and health sciences Molecular dynamics Structural Biology Molecule Humans Amino Acid Sequence Molecular Biology biology Chemistry General Medicine 030104 developmental biology Multiprotein Complexes Biophysics Molecular mechanism biology.protein Thermodynamics Calcium Hydrophobic and Hydrophilic Interactions Protein Binding |
| DOI: | 10.6084/m9.figshare.5592790 |
| Popis: | Molecular understanding of bio-macromolecular binding is a challenging task due to large sizes of the molecules and presence of variety of interactions. Here, we study the molecular mechanism of calmodulin (CaM) binding to Orai1 that regulates Ca2+-dependent inactivation process in eukaryotic cells. Although experimental observations indicate that Orai1 binds to the C-terminal of Ca2+-loaded CaM, it is not decisive if N-domain of CaM interacts with Orai1. We address the issue of interaction of different domains of CaM with Orai1 using conformational thermodynamic changes, computed from histograms of dihedral angles over simulated trajectories of CaM, CaM-binding domain of Orai1 and complexes of CaM with Orai1. The changes for all residues of both C and N terminal domains of CaM upon Orai1 binding are compared. Our analysis shows that Orai1binds to both C-terminal and N-terminal domains of CaM, indicating 1:2 stoichiometry. The Orai1 binding to N-terminal domain of CaM is less stable than that to the C-terminal domain. The binding residues are primarily hydrophobic. These observations are in qualitative agreement to the experiments. The conformational thermodynamic changes thus provide a useful computational tool to provide atomic details of interactions in bio-macromolecular binding. |
| Databáze: | OpenAIRE |
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