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Updated: Jul 5, 2025
Crystal Structure of the N-terminal Domain of Ryanodine Receptor from Plutella xylostella
Published on: November 30, 2018
Optimization of CHARMM force field parameters for ryanodine receptor inhibitory drug dantrolene using FFTK and
Saliha Nur Uludag1, Cemil Can Saylan1,2, Adem Tekin1,3
1Computational Science and Engineering Department, Informatics Institute, Istanbul Technical University, Ayazaga Campus, Maslak, 34469, Istanbul, Türkiye.
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.
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