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

Saliha Nur Uludağ; Cemil Can Saylan; Adem Tekin; Sefer Baday

doi:10.1007/s00894-024-05841-3

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

Saliha Nur Uludağ, Cemil Can Saylan, Adem Tekin, Sefer Baday^*

^*Bu çalışma için yazışmadan sorumlu yazar

Bilişim Enstitüsü

Araştırma sonucu: Dergiye katkı › Makale › bilirkişi

3 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 dil	İngilizce
Makale numarası	46
Dergi	Journal of Molecular Modeling
Hacim	30
Basın numarası	2
DOI'lar	https://doi.org/10.1007/s00894-024-05841-3
Yayın durumu	Yayınlandı - 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.

Finansörler	Finansör 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 Üniversitesi	5009062021
Türkiye Bilimsel ve Teknolojik Araştırma Kurumu	:119Z578

Belgeye Erişim

10.1007/s00894-024-05841-3

Diğer Dosyalar ve Linkler

Link to publication in Scopus

Alıntı Yap

@article{5e6532440b1e43afac8ce15ed91250fc,

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

abstract = "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.",

keywords = "Dantrolene, FFParam, FFTK, Force field, Ryanodine receptor",

author = "Uludağ, {Saliha Nur} and Saylan, {Cemil Can} and Adem Tekin and Sefer Baday",

note = "Publisher Copyright: {\textcopyright} 2024, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.",

year = "2024",

month = feb,

doi = "10.1007/s00894-024-05841-3",

language = "English",

volume = "30",

journal = "Journal of Molecular Modeling",

issn = "1610-2940",

publisher = "Springer Science and Business Media Deutschland GmbH",

number = "2",

}

TY - JOUR

T1 - Optimization of CHARMM force field parameters for ryanodine receptor inhibitory drug dantrolene using FFTK and FFParam

AU - Uludağ, Saliha Nur

AU - Saylan, Cemil Can

AU - Tekin, Adem

AU - Baday, Sefer

PY - 2024/2

Y1 - 2024/2

N2 - 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.

AB - 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.

KW - Dantrolene

KW - FFParam

KW - FFTK

KW - Force field

KW - Ryanodine receptor

UR - http://www.scopus.com/inward/record.url?scp=85182856906&partnerID=8YFLogxK

U2 - 10.1007/s00894-024-05841-3

DO - 10.1007/s00894-024-05841-3

M3 - Article

C2 - 38261112

AN - SCOPUS:85182856906

SN - 1610-2940

VL - 30

JO - Journal of Molecular Modeling

JF - Journal of Molecular Modeling

IS - 2

M1 - 46

ER -

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

Özet

Bibliyografik not

Finansman

Belgeye Erişim

Diğer Dosyalar ve Linkler

Parmak izi

Alıntı Yap