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Hepatitis C virus NS5B polymerase: QM/MM calculations show the important role of the internal energy in ligand binding.

Publication ,  Journal Article
Parks, JM; Kondru, RK; Hu, H; Beratan, DN; Yang, W
Published in: The journal of physical chemistry. B
March 2008

The inter- and intramolecular interactions that determine the experimentally observed binding mode of the ligand (2Z)-2-(benzoylamino)-3-[4-(2-bromophenoxy)phenyl]-2-propenoate in complex with hepatitis C virus NS5B polymerase have been studied using QM/MM calculations. DFT-based QM/MM optimizations were performed on a number of ligand conformers in the protein-ligand complex. Using these initial poses, our aim is 2-fold. First, we identify the minimum energy pose. Second, we dissect the energetic contributions to this pose using QM/MM methods. The study reveals the critical importance of internal energy for the proper energy ranking of the docked poses. Using this protocol, we successfully identified three poses that have low RMSD with respect to the crystallographic structure from among the top 20 initially docked poses. We show that the most important energetic component contributing to binding for this particular protein-ligand system is the conformational (i.e., QM internal) energy.

Duke Scholars

Published In

The journal of physical chemistry. B

DOI

EISSN

1520-5207

ISSN

1520-6106

Publication Date

March 2008

Volume

112

Issue

10

Start / End Page

3168 / 3176

Related Subject Headings

  • Water
  • Viral Nonstructural Proteins
  • RNA-Dependent RNA Polymerase
  • Protein Binding
  • Molecular Structure
  • Models, Molecular
  • Ligands
  • Crystallography, X-Ray
  • Binding Sites
  • 51 Physical sciences
 

Citation

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Parks, J. M., Kondru, R. K., Hu, H., Beratan, D. N., & Yang, W. (2008). Hepatitis C virus NS5B polymerase: QM/MM calculations show the important role of the internal energy in ligand binding. The Journal of Physical Chemistry. B, 112(10), 3168–3176. https://doi.org/10.1021/jp076885j
Parks, Jerry M., Rama K. Kondru, Hao Hu, David N. Beratan, and Weitao Yang. “Hepatitis C virus NS5B polymerase: QM/MM calculations show the important role of the internal energy in ligand binding.The Journal of Physical Chemistry. B 112, no. 10 (March 2008): 3168–76. https://doi.org/10.1021/jp076885j.
Parks JM, Kondru RK, Hu H, Beratan DN, Yang W. Hepatitis C virus NS5B polymerase: QM/MM calculations show the important role of the internal energy in ligand binding. The journal of physical chemistry B. 2008 Mar;112(10):3168–76.
Parks, Jerry M., et al. “Hepatitis C virus NS5B polymerase: QM/MM calculations show the important role of the internal energy in ligand binding.The Journal of Physical Chemistry. B, vol. 112, no. 10, Mar. 2008, pp. 3168–76. Epmc, doi:10.1021/jp076885j.
Parks JM, Kondru RK, Hu H, Beratan DN, Yang W. Hepatitis C virus NS5B polymerase: QM/MM calculations show the important role of the internal energy in ligand binding. The journal of physical chemistry B. 2008 Mar;112(10):3168–3176.
Journal cover image

Published In

The journal of physical chemistry. B

DOI

EISSN

1520-5207

ISSN

1520-6106

Publication Date

March 2008

Volume

112

Issue

10

Start / End Page

3168 / 3176

Related Subject Headings

  • Water
  • Viral Nonstructural Proteins
  • RNA-Dependent RNA Polymerase
  • Protein Binding
  • Molecular Structure
  • Models, Molecular
  • Ligands
  • Crystallography, X-Ray
  • Binding Sites
  • 51 Physical sciences