Molecular dynamics assessment of mechanical properties of the thin filaments in cardiac muscle

Koubassova, N.A.; Tsaturyan, A.K.

Авторы: Koubassova N.A., Tsaturyan A.K.
Журнал: International Journal of Molecular Sciences
Том: 24
Номер: 5
Год издания: 2023
Издательство: MDPI
Местоположение издательства: Basel, Switzerland
Первая страница: 4792
Последняя страница: 0
DOI: 10.3390/ijms24054792
Аннотация: Contraction of cardiac muscle is regulated by Ca 2 + ions via regulatory proteins, troponin(Tn), and tropomyosin (Tpm) associated with the thin (actin) filaments in myocardial sarcomeres.The binding of Ca 2 + to a Tn subunit causes mechanical and structural changes in the multiproteinregulatory complex. Recent cryo-electron microscopy (cryo-EM) models of the complex allow one tostudy the dynamic and mechanical properties of the complex using molecular dynamics (MD). Herewe describe two refined models of the thin filament in the calcium-free state that include protein frag-ments unresolved by cryo-EM and reconstructed using structure prediction software. The parametersof the actin helix and the bending, longitudinal, and torsional stiffness of the filaments estimated fromthe 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 byimproving the protein–protein interaction in some regions of the complex. The use of relatively longrefined models of the regulatory complex of the thin filament allows one to perform MD simulation ofthe molecular mechanism of Ca 2 + regulation of contraction without additional constraints and studythe effects of cardiomyopathy-associated mutation of the thin filament proteins of cardiac muscle.
Добавил в систему: Кубасова Наталия Алексеевна

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Molecular dynamics assessment of mechanical properties of the thin filaments in cardiac muscleстатья

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