Molecular Dynamics Assessment of Mechanical Properties of the Thin Filaments in Cardiac Muscle.
Int J Mol Sci
; 24(5)2023 Mar 01.
Article
en En
| MEDLINE
| ID: mdl-36902223
ABSTRACT
Contraction of cardiac muscle is regulated by Ca2+ ions via regulatory proteins, troponin (Tn), and tropomyosin (Tpm) associated with the thin (actin) filaments in myocardial sarcomeres. The binding of Ca2+ to a Tn subunit causes mechanical and structural changes in the multiprotein regulatory complex. Recent cryo-electron microscopy (cryo-EM) models of the complex allow one to study the dynamic and mechanical properties of the complex using molecular dynamics (MD). Here we describe two refined models of the thin filament in the calcium-free state that include protein fragments unresolved by cryo-EM and reconstructed using structure prediction software. The parameters of the actin helix and the bending, longitudinal, and torsional stiffness of the filaments estimated from the MD simulations performed with these models were close to those found experimentally. However, problems revealed from the MD simulation suggest that the models require further refinement by improving the protein-protein interaction in some regions of the complex. The use of relatively long refined models of the regulatory complex of the thin filament allows one to perform MD simulation of the molecular mechanism of Ca2+ regulation of contraction without additional constraints and study the effects of cardiomyopathy-associated mutation of the thin filament proteins of cardiac muscle.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Sarcómeros
/
Citoesqueleto de Actina
/
Simulación de Dinámica Molecular
/
Miocardio
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Int J Mol Sci
Año:
2023
Tipo del documento:
Article
País de afiliación:
Rusia