Optimization of CHARMM force field parameters for ryanodine receptor inhibitory drug dantrolene using FFTK and FFParam

Saliha Nur Akcay, Cemil Can Saylan, Adem Tekin, Sefer Baday*

*Bu çalışma için yazışmadan sorumlu yazar

Araştırma sonucu: ???type-name???Makalebilirkişi

1 Atıf (Scopus)

Özet

Context: Ryanodine receptors (RyRs) are large intracellular ligand-gated calcium release ion channels. Mutations in human RyR1 in combination with a volatile anesthetic or muscle relaxant are known to cause leaky RyRs resulting in malignant hyperthermia (MH). This has long been primarily treated with the RyR inhibitory drug dantrolene. Alternatives to dantrolene as a RyR inhibitor may be found through computer-aided drug design. Additionally, molecular dynamics (MD) studies of dantrolene interacting with RyRs may reveal its full mechanism of action. The availability of accurate force field parameters is important for the success of both. Methods: In this study, force field parameters for dantrolene were obtained from the CHARMM General Force Field (CGenFF) program and optimized using the force field toolkit (FFTK) and FFParam programs. The obtained parameters were then validated by a comparison between calculated and experimental IR spectra and normal mode analysis, among other techniques.

Orijinal dilİngilizce
Makale numarası46
DergiJournal of Molecular Modeling
Hacim30
Basın numarası2
DOI'lar
Yayın durumuYayınlandı - Şub 2024

Bibliyografik not

Publisher Copyright:
© 2024, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Finansman

This work was supported by the Turkish-Slovak Joint Partnership of The Scientific and Technological Research Council of Turkey (TUBITAK) [Grant Agreement Number:119Z578]. Computing resources used in this work were provided by the National Center for High Performance Computing of Turkey (UHeM) under grant number 5009062021.

FinansörlerFinansör numarası
National Center for High Performance Computing of Turkey
Turkish-Slovak Joint Partnership of The Scientific and Technological Research Council of Turkey
Ulusal Yüksek Başarımlı Hesaplama Merkezi, Istanbul Teknik Üniversitesi5009062021
Türkiye Bilimsel ve Teknolojik Araştırma Kurumu:119Z578

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