Structural Survey of Zinc-Containing Proteins and Development of the Zinc AMBER Force Field (ZAFF)
Open accessAbstract
Currently the Protein Data Bank (PDB) contains over 18,000 structures that contain a metal ion including Na, Mg, K, Ca, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Pd, Ag, Cd, Ir, Pt, Au, and Hg. In general, carrying out classical molecular dynamics (MD) simulations of metalloproteins is a convoluted and time consuming process. Herein, we describe MCPB (Metal Center Parameter Builder), which allows one, to conveniently and rapidly incorporate metal ions using the bonded plus electrostatics model (Hoops et al., J. Am. Chem. Soc. 1991, 113, 8262-8270) into the AMBER Force Field (FF). MCPB was used to develop a Zinc FF, ZAFF, which is compatible with the existing AMBER FFs. The PDB was mined for all Zn containing structures with most being tetrahedrally bound. The most abundant primary shell ligand combinations were extracted and FFs were created. These include Zn bound to CCCC, CCCH, CCHH, CHHH, HHHH, HHHO, HHOO, HOOO, HHHD, and HHDD (O = water and the remaining are 1 letter amino acid codes). Bond and angle force constants and RESP charges were obtained from B3LYP/6-31G* calculations of model structures from the various primary shell combinations. MCPB and ZAFF can be used to create FFs for MD simulations of metalloproteins to study enzyme catalysis, drug design and metalloprotein crystal refinement.
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Bonded models, such as the Zinc AMBER Force Field, represent tetrahedral coordination with harmonic potentials and angle terms for an explicit bond, giving directionality.
“Bonded models, such as the Zinc AMBER Force Field,23 describe the tetrahedral coordination with harmonic potentials and angle terms for an explicit bond that provides directionality.”
From AutoDock4<sub>Zn</sub>: An Improved AutoDock Force Field for Small-Molecule Docking to Zinc Metalloproteins (2014) · cites this paper as [23]
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- Authors
- Peters, M. B., Yang, Y., Wang, B., Füsti-Molnár, L., Weaver, M. N., & Merz, K. M.
- Affiliations
- University of Florida (US)
- Corresponding author
- Merz, Kenneth M.
- Venue
- Journal of Chemical Theory and Computation
- Publisher
- American Chemical Society (ACS)
- Published
- 2010-08-25
- Volume
- 6
- Issue
- 9
- Pages
- 2935-2947
- ISSN
- 1549-9618 (ISSN-L)
- 1549-9626
- PMC
- PMC2941202
- OpenAlex
- W2010076108
- Cited by
- 501
- References
- 71
- Citations by year
- 2026: 32 · 2025: 43 · 2024: 46 · 2023: 49 · 2022: 49 · 2021: 48 · 2020: 32 · 2019: 36 · 2018: 31 · 2017: 24 · 2016: 19 · 2015: 26 · 2014: 24 · 2013: 21 · 2012: 13
- FWCI
- 5.43
- 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 (R01GM066859, R01GM044974)
- 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-containing proteins, metalloproteins, force field parameterization, metal ion binding, tetrahedral zinc coordination, MCPB, enzyme catalysis
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