Functional Calmodulin States are Selected from an Electrostatically Tuned Free Energy Landscape
Tayhan, B.; Horozoglu, S.; Atilgan, A. R.; Atilgan, C.
Show abstract
Calmodulin (CaM) is a versatile calcium-binding protein whose structural flexibility enables regulation of diverse cellular processes. Capturing its full conformational landscape remains challenging due to high energy barriers between states. Here we employ well-tempered metadynamics simulations using key collective variables to explore CaM conformations under calcium-bound and calcium-free states at physiological and low salt concentrations. We identify four principal conformations that shift in population depending on calcium binding and ionic strength. Calcium binding favors compact states, while low salt conditions flatten the energy landscape, facilitating transitions, but also causing kinetic trapping due to salt-bridge interactions. Comparison with experimental CaM-protein complexes reveals that target binding stabilizes extended conformations distinct from minima accessible to free CaM. These findings elucidate how calcium and ionic environment orchestrate CaMs conformational dynamics, enhancing understanding of its functional adaptability in cellular calcium signaling.
Matching journals
The top 5 journals account for 50% of the predicted probability mass.
Similar papers in this journal
Similar papers in this journal
- How minor sequence changes enable mechanistic diversity in MFS transporters? An atomic-level rationale for symport emergence in NarU 96%
- Covalent adducts formed by the androgen receptor transactivation domain and small molecule drugs remain disordered 96%
- Decoding protein-membrane binding interfaces from surface-fingerprint-based geometric deep learning and molecular dynamics simulations 96%
Similar papers in this journal
- Folding-upon-binding pathways of an intrinsically disordered protein from a deep Markov state model 96%
- Integrating comparative modeling and accelerated simulations reveals conformational and energetic basis of actomyosin force generation 96%
- The molecular mechanism of lipid uptake by membrane-anchored bridge-like lipid transfer proteins. 95%
Similar papers in this journal
- Potassium dependent structural changes in the selectivity filter of HERG potassium channels 96%
- Lipid-mediated organization of prestin in the outer hair cell membrane and its implications in sound amplification 95%
- Physics-based inverse design of cholesterolattracting transmembrane helices reveals aparadoxical role of hydrophobic length 95%
Similar papers in this journal
- An Allosteric Cholesterol Site in Glycine Receptors Characterized Through Molecular Simulations 96%
- Unfolding and Translocation of Knotted Proteins by Clp Biological Nanomachines: Synergistic Contribution of Primary Sequence and Topology Revealed by Molecular Dynamics Simulations 96%
- Structural preferences shape the entropic force of disordered protein ensembles 96%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.