Mebendazole's Conformational Space and Its Predicted Binding to Human Heat-Shock Protein 90

Walter Fiedler; Fabian Freisleben; Jasmin Wellbrock; Karl N Kirschner

doi:10.1021/acs.jcim.2c00290

Mebendazole's Conformational Space and Its Predicted Binding to Human Heat-Shock Protein 90

Standard

Mebendazole's Conformational Space and Its Predicted Binding to Human Heat-Shock Protein 90. / Fiedler, Walter; Freisleben, Fabian; Wellbrock, Jasmin; Kirschner, Karl N.

in: J CHEM INF MODEL, Jahrgang 62, Nr. 15, 08.08.2022, S. 3604-3617.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Fiedler, W, Freisleben, F, Wellbrock, J & Kirschner, KN 2022, 'Mebendazole's Conformational Space and Its Predicted Binding to Human Heat-Shock Protein 90', J CHEM INF MODEL, Jg. 62, Nr. 15, S. 3604-3617. https://doi.org/10.1021/acs.jcim.2c00290

APA

Fiedler, W., Freisleben, F., Wellbrock, J., & Kirschner, K. N. (2022). Mebendazole's Conformational Space and Its Predicted Binding to Human Heat-Shock Protein 90. J CHEM INF MODEL, 62(15), 3604-3617. https://doi.org/10.1021/acs.jcim.2c00290

Vancouver

Fiedler W, Freisleben F, Wellbrock J, Kirschner KN. Mebendazole's Conformational Space and Its Predicted Binding to Human Heat-Shock Protein 90. J CHEM INF MODEL. 2022 Aug 8;62(15):3604-3617. https://doi.org/10.1021/acs.jcim.2c00290

Bibtex

@article{c9b1ece42a7f4c3487be3670ba06ba3a,

title = "Mebendazole's Conformational Space and Its Predicted Binding to Human Heat-Shock Protein 90",

abstract = "Recent experimental evidence suggests that mebendazole, a popular antiparasitic drug, binds to heat shock protein 90 (Hsp90) and inhibits acute myeloid leukemia cell growth. In this study we use quantum mechanics (QM), molecular similarity, and molecular dynamics (MD) calculations to predict possible binding poses of mebendazole to the adenosine triphosphate (ATP) binding site of Hsp90. Extensive conformational searches and minimization of the five mebendazole tautomers using the MP2/aug-cc-pVTZ theory level resulted in 152 minima. Mebendazole-Hsp90 complex models were subsequently created using the QM optimized conformations and protein coordinates obtained from experimental crystal structures that were chosen through similarity calculations. Nine different poses were identified from a total of 600 ns of explicit solvent, all-atom MD simulations using two different force fields. All simulations support the hypothesis that mebendazole is able to bind to the ATP binding site of Hsp90.",

author = "Walter Fiedler and Fabian Freisleben and Jasmin Wellbrock and Kirschner, {Karl N}",

year = "2022",

month = aug,

day = "8",

doi = "10.1021/acs.jcim.2c00290",

language = "English",

volume = "62",

pages = "3604--3617",

journal = "J CHEM INF MODEL",

issn = "1549-9596",

publisher = "American Chemical Society",

number = "15",

}

RIS

TY - JOUR

T1 - Mebendazole's Conformational Space and Its Predicted Binding to Human Heat-Shock Protein 90

AU - Fiedler, Walter

AU - Freisleben, Fabian

AU - Wellbrock, Jasmin

AU - Kirschner, Karl N

PY - 2022/8/8

Y1 - 2022/8/8

N2 - Recent experimental evidence suggests that mebendazole, a popular antiparasitic drug, binds to heat shock protein 90 (Hsp90) and inhibits acute myeloid leukemia cell growth. In this study we use quantum mechanics (QM), molecular similarity, and molecular dynamics (MD) calculations to predict possible binding poses of mebendazole to the adenosine triphosphate (ATP) binding site of Hsp90. Extensive conformational searches and minimization of the five mebendazole tautomers using the MP2/aug-cc-pVTZ theory level resulted in 152 minima. Mebendazole-Hsp90 complex models were subsequently created using the QM optimized conformations and protein coordinates obtained from experimental crystal structures that were chosen through similarity calculations. Nine different poses were identified from a total of 600 ns of explicit solvent, all-atom MD simulations using two different force fields. All simulations support the hypothesis that mebendazole is able to bind to the ATP binding site of Hsp90.

AB - Recent experimental evidence suggests that mebendazole, a popular antiparasitic drug, binds to heat shock protein 90 (Hsp90) and inhibits acute myeloid leukemia cell growth. In this study we use quantum mechanics (QM), molecular similarity, and molecular dynamics (MD) calculations to predict possible binding poses of mebendazole to the adenosine triphosphate (ATP) binding site of Hsp90. Extensive conformational searches and minimization of the five mebendazole tautomers using the MP2/aug-cc-pVTZ theory level resulted in 152 minima. Mebendazole-Hsp90 complex models were subsequently created using the QM optimized conformations and protein coordinates obtained from experimental crystal structures that were chosen through similarity calculations. Nine different poses were identified from a total of 600 ns of explicit solvent, all-atom MD simulations using two different force fields. All simulations support the hypothesis that mebendazole is able to bind to the ATP binding site of Hsp90.

U2 - 10.1021/acs.jcim.2c00290

DO - 10.1021/acs.jcim.2c00290

M3 - SCORING: Journal article

C2 - 35867562

VL - 62

SP - 3604

EP - 3617

JO - J CHEM INF MODEL

JF - J CHEM INF MODEL

SN - 1549-9596

IS - 15

ER -