A Point-Charge Force Field for Molecular Mechanics Simulations of Proteins Based on Condensed-Phase Quantum Mechanical Calculations

Yong Duan, Chun Wu, Shibasish Chowdhury, Mathew C. Lee, Guoming Xiong, Wei Zhang, Rong Yang, Piotr Cieplak, Ray Luo, Taisung Lee, James Caldwell, Junmei Wang, Peter Kollman

Research output: Contribution to journalArticle

3110 Citations (Scopus)

Abstract

Molecular mechanics models have been applied extensively to study the dynamics of proteins and nucleic acids. Here we report the development of a third-generation point-charge all-atom force field for proteins. Following the earlier approach of Cornell et al., the charge set was obtained by fitting to the electrostatic potentials of dipeptides calculated using B3LYP/cc-pVTZ//HF/6-31G** quantum mechanical methods. The main-chain torsion parameters were obtained by fitting to the energy profiles of Ace-Ala-Nme and Ace-Gly-Nme di-peptides calculated using MP2/cc-pVTZ//HF/6-31G** quantum mechanical methods. All other parameters were taken from the existing AMBER data base. The major departure from previous force fields is that all quantum mechanical calculations were done in the condensed phase with continuum solvent models and an effective dielectric constant of ε = 4. We anticipate that this force field parameter set will address certain critical short comings of previous force fields in condensed-phase simulations of proteins. Initial tests on peptides demonstrated a high-degree of similarity between the calculated and the statistically measured Ramanchandran maps for both Ace-Gly-Nme and Ace-Ala-Nme di-peptides. Some highlights of our results include (1) well-preserved balance between the extended and helical region distributions, and (2) favorable type-II poly-proline helical region in agreement with recent experiments. Backward compatibility between the new and Cornell et al. charge sets, as judged by overall agreement between dipole moments, allows a smooth transition to the new force field in the area of ligand-binding calculations. Test simulations on a large set of proteins are also discussed.

Original languageEnglish (US)
Pages (from-to)1999-2012
Number of pages14
JournalJournal of Computational Chemistry
Volume24
Issue number16
DOIs
StatePublished - Dec 2003

Fingerprint

Molecular Mechanics
Molecular mechanics
Force Field
Charge
Peptides
Proteins
Protein
Simulation
Dipeptides
Nucleic acids
Dipole moment
Proline
Torsional stress
Nucleic Acids
Dielectric Constant
Electrostatics
Permittivity
Large Set
Compatibility
Ligands

Keywords

  • Molecular mechanics simulations
  • Point-charge force field
  • Quantum mechanical calculations

ASJC Scopus subject areas

  • Chemistry(all)
  • Safety, Risk, Reliability and Quality

Cite this

A Point-Charge Force Field for Molecular Mechanics Simulations of Proteins Based on Condensed-Phase Quantum Mechanical Calculations. / Duan, Yong; Wu, Chun; Chowdhury, Shibasish; Lee, Mathew C.; Xiong, Guoming; Zhang, Wei; Yang, Rong; Cieplak, Piotr; Luo, Ray; Lee, Taisung; Caldwell, James; Wang, Junmei; Kollman, Peter.

In: Journal of Computational Chemistry, Vol. 24, No. 16, 12.2003, p. 1999-2012.

Research output: Contribution to journalArticle

Duan, Y, Wu, C, Chowdhury, S, Lee, MC, Xiong, G, Zhang, W, Yang, R, Cieplak, P, Luo, R, Lee, T, Caldwell, J, Wang, J & Kollman, P 2003, 'A Point-Charge Force Field for Molecular Mechanics Simulations of Proteins Based on Condensed-Phase Quantum Mechanical Calculations', Journal of Computational Chemistry, vol. 24, no. 16, pp. 1999-2012. https://doi.org/10.1002/jcc.10349
Duan, Yong ; Wu, Chun ; Chowdhury, Shibasish ; Lee, Mathew C. ; Xiong, Guoming ; Zhang, Wei ; Yang, Rong ; Cieplak, Piotr ; Luo, Ray ; Lee, Taisung ; Caldwell, James ; Wang, Junmei ; Kollman, Peter. / A Point-Charge Force Field for Molecular Mechanics Simulations of Proteins Based on Condensed-Phase Quantum Mechanical Calculations. In: Journal of Computational Chemistry. 2003 ; Vol. 24, No. 16. pp. 1999-2012.
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AU - Chowdhury, Shibasish

AU - Lee, Mathew C.

AU - Xiong, Guoming

AU - Zhang, Wei

AU - Yang, Rong

AU - Cieplak, Piotr

AU - Luo, Ray

AU - Lee, Taisung

AU - Caldwell, James

AU - Wang, Junmei

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