Optimization of CHARMM force field parameters of a prostate cancer drug enzalutamide

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4 Citations (Scopus)


Enzalutamide is the most recent and potent clinically available drug molecule used to treat castration-resistant metastatic prostate cancer patients. In the presence of certain mutations on the Androgen receptor, enzalutamide fails to function as an antagonist. The molecular mechanism of this resistance has not been understood clearly. Molecular Dynamics (MD) simulations are a powerful tool to investigate such resistance mechanisms. Insights from MD simulations of receptor-ligand complex heavily depend on the quality of the parameters of the ligands. Thus, we developed and optimized CHARMM Force field parameters of enzalutamide. The initial assignment of parameters was done by using the CHARMM General Force Field (CGenFF) program. After that, using the Force Field Tool Kit (FFTK) partial charges, bond, angle and dihedral parameters of enzalutamide were optimized to reproduce quantum mechanics calculation results. For the validation of parameters, water-octanol partition coefficient, Infrared Spectra (IR) and normal mode analysis calculations were performed. In addition, a 300 ns-long MD simulation of enzalutamide was carried out to assess the ability of the optimized parameters in exploring torsional angle space.

Original languageEnglish
Article number107541
JournalJournal of Molecular Graphics and Modelling
Publication statusPublished - May 2020

Bibliographical note

Publisher Copyright:
© 2020 Elsevier Inc.


This work has been funded by the Career Development Program ( 3501 ) of The Scientific and Technological Research Council of Turkey (TUBITAK) (Grant Agreement Number: 117Z353 ). Calculations reported in this work were performed at National Center for High Performance Computing of Turkey (UHeM).

FundersFunder number
Türkiye Bilimsel ve Teknolojik Araştirma Kurumu


    • Androgen receptor
    • CHARMM
    • Enzalutamide
    • FFTK
    • Parameterization


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