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Title: Development of CHARMM-Compatible Force-Field Parameters for Cobalamin and Related Cofactors from Quantum Mechanical Calculations

Journal Article · · Journal of Chemical Theory and Computation
 [1]; ORCiD logo [2]; ORCiD logo [1]
  1. Georgia Inst. of Technology, Atlanta, GA (United States)
  2. Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
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Corrinoid cofactors such as cobalamin are used by many enzymes and are essential for most living organisms. Therefore, there is broad interest in investigating cobalamin–protein interactions with molecular dynamics simulations. Previously developed parameters for cobalamins are based mainly on crystal structure data. Here, we report CHARMM-compatible force field parameters for several corrinoids developed from quantum mechanical calculations. We provide parameters for corrinoids in three oxidation states, Co3+, Co2+, and Co1+, and with various axial ligands. Lennard-Jones parameters for the cobalt center in the Co(II) and Co(I) states were optimized using a helium atom probe, and partial atomic charges were obtained with a combination of natural population analysis (NPA) and restrained electrostatic potential (RESP) fitting approaches. The Force Field Toolkit was used to optimize all bonded terms. The resulting parameters, determined solely from calculations of cobalamin alone or in water, were then validated by assessing their agreement with density functional theory geometries and by analyzing molecular dynamics simulation trajectories of several corrinoid proteins for which X-ray crystal structures are available. In each case, we obtained excellent agreement with the reference data. In comparison to previous CHARMM-compatible parameters for cobalamin, we observe a better agreement for the fold angle and lower RMSD in the cobalamin binding site. The approach described here is readily adaptable for developing CHARMM-compatible force-field parameters for other corrinoids or large biomolecules.

Research Organization:
Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). National Energy Research Scientific Computing Center (NERSC)
Sponsoring Organization:
USDOE Office of Science (SC), Biological and Environmental Research (BER)
Grant/Contract Number:
AC05-00OR22725; AC02-05CH11231
OSTI ID:
1459308
Alternate ID(s):
OSTI ID: 1480247
Journal Information:
Journal of Chemical Theory and Computation, Vol. 14, Issue 2; ISSN 1549-9618
Publisher:
American Chemical SocietyCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 15 works
Citation information provided by
Web of Science

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Cited By (3)

Recent Advances in Coarse-Grained Models for Biomolecules and Their Applications journal August 2019
Atomistic Simulations of COSAN: Amphiphiles without a Head‐and‐Tail Design Display “Head and Tail” Surfactant Behavior journal January 2020
Atomistic Simulations of COSAN: Amphiphiles without a Head‐and‐Tail Design Display “Head and Tail” Surfactant Behavior journal February 2020

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