A Transferable Nonbonded Pairwise Force Field to Model Zinc Interactions in Metalloproteins

Wu, Ruibo; Lu, Zhenyu; Cao, Zexing; Zhang, Yingkai

doi:10.1021/ct100525r

Cited by 53Protein Structure and DynamicsAdvanced Chemical Physics StudiesAdvanced Physical and Chemical Molecular Interactions

A Transferable Nonbonded Pairwise Force Field to Model Zinc Interactions in Metalloproteins

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Wu, Ruibo, Lu, Zhenyu, Cao, Zexing, Zhang, Yingkai·2011·Journal of Chemical Theory and Computation

DOI 10.1021/ct100525rPMC PMC3087386

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Abstract

Herein we introduce a novel practical strategy to overcome the well-known challenge of modeling the divalent zinc cation in metalloproteins. The main idea is to design short-long effective functions (SLEF) to describe charge interactions between the zinc ion and all other atoms. This SLEF approach has the following desired features: (1). It is pairwise, additive and compatible with widely used atomic pair-wise force fields for modeling biomolecules; (2). It only changes interactions between the zinc ion and other atoms, and does not affect force field parameters that model other interactions in the system; (3). It is a non-bonded model that is inherently capable to describe different zinc ligands and coordination modes. By optimizing two SLEF parameters as well as zinc vdW parameters through force matching based on Born-Oppenheimer ab initio QM/MM molecular dynamics simulations, we have successfully developed the first SLEF force field (SLEF1) to describe zinc interactions. Extensive molecular dynamics simulations of seven zinc enzyme systems with different coordination ligands and distinct chelation modes (4-,5-,6-fold), including the binuclear zinc active site, yielded zinc coordination numbers and binding distances in good agreement with the corresponding crystal structures as well as ab initio QM/MM MD results. This not only demonstrates the transferability and adequacy of the new SLEF1 force field in describing a variety of zinc proteins, but also indicates that this novel SLEF approach is a promising direction to explore for improving force field description of metal ion interactions.

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That nonbonded description depends on assigned partial charges, so its accuracy is strongly tied to the charge model chosen.
“This description relies on assignment of partial charges,11−13 and thus accuracy becomes strongly dependent on the choice of charge model.”
From AutoDock4Zn: An Improved AutoDock Force Field for Small-Molecule Docking to Zinc Metalloproteins (2014) · cites this paper as [12]
The Methods section defines the nonbonded SLEF interaction using the zinc charge and each other atom’s MM charge; the Discussion says its behavior varies with charge magnitude. The paper does not establish that accuracy is strongly dependent on the choice of charge model. Its Introduction instead identifies the conventional 1/r interaction form as the main deficiency of existing nonbonded models. No page numbers are available in our copy. (LLM, conf=0.82)
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Authors: Wu, R., Lu, Z., Cao, Z., & Zhang, Y.
Affiliations: Xiamen University (CN)
Corresponding author: Zhang, Yingkai
ORCID: Wu, Ruibo
Lu, Zhenyu
Cao, Zexing
Zhang, Yingkai
Venue: Journal of Chemical Theory and Computation
Publisher: American Chemical Society (ACS)
Published: 2010-12-23
Volume: 7
Issue: 2
Pages: 433-443
ISSN: 1549-9618 (ISSN-L)
1549-9626
DOI: 10.1021/ct100525r
PMC: PMC3087386
OpenAlex: W2049623642
Cited by: 53
References: 72
Citations by year: 2026: 2 · 2025: 2 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 1 · 2020: 4 · 2019: 7 · 2018: 5 · 2017: 4 · 2016: 1 · 2015: 6 · 2014: 5 · 2013: 9 · 2012: 3
FWCI: 1.69
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Journal of Chemical Theory and Computation (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Institute of General Medical Sciences (R01GM079223)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
Physical Sciences › Physics and Astronomy › Atomic and Molecular Physics, and Optics › Advanced Chemical Physics Studies
Physical Sciences › Chemistry › Physical and Theoretical Chemistry › Advanced Physical and Chemical Molecular Interactions
Keywords: zinc ions, metalloproteins, zinc metalloenzyme, force field parameterization, QM/MM molecular dynamics, force matching, transferable force fields

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A Transferable Nonbonded Pairwise Force Field to Model Zinc Interactions in Metalloproteins

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