Work

Functional Calmodulin States Are Selected from an Electrostatically Tuned Free Energy Landscape

Year: 2026

Type: article

Abstract: Calmodulin (CaM) is a versatile calcium-binding protein whose structural flexibility enables regulation of diverse cellular processes, but capturing its full conformational landscape remains challenging due to high energy barriers between states. Here we employ well-tempered metadynamics simulations using physically interpretable 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 shows that target binding stabilizes extended conformations distinct from the minima accessible to free CaM, illuminating how calcium and the ionic environment orchestrate CaM's conformational dynamics in cellular signaling.

Source: Journal of Chemical Information and Modeling

DOI: 10.1021/acs.jcim.6c00532

Authors: Busra Tayhan, Sila Horozoglu, Ali Rana Atilgan, Canan Atilgan

Institution: Sabancı Üniversitesi

Language: English

Topic: Protein Structure and Dynamics

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: hybrid

Estimated APC paid: $4,500

Funder: Türkiye Bilimsel ve Teknolojik Araştırma Kurumu