Force Field Development and Molecular Dynamics of [NiFe] Hydrogenase
Classical molecular force-field parameters describing the structure and motion of metal clusters in [NiFe] hydrogenase enzymes can be used to compare the dynamics and thermodynamics of [NiFe] under different oxidation, protonation, and ligation circumstances. Using density functional theory (DFT) calculations of small model clusters representative of the active site and the proximal, medial, and distal Fe/S metal centers and their attached protein side chains, we have calculated classical force-field parameters for [NiFe] in reduced and oxidized states, including internal coordinates, force constants, and atom-centered charges. Derived force constants revealed that cysteinate ligands bound to the metal ions are more flexible in the Ni-B active site, which has a bridging hydroxide ligand, than in the Ni-C active site, which has a bridging hydride. Ten nanosecond all-atom, explicit-solvent MD simulations of [NiFe] hydrogenase in oxidized and reduced catalytic states established the stability of the derived force-field parameters in terms of C{alpha} and metal cluster fluctuations. Average active site structures from the protein MD simulations are consistent with [NiFe] structures from the Protein Data Bank, suggesting that the derived force-field parameters are transferrable to other hydrogenases beyond the structure used for testing. A comparison of experimental H{sub 2}-production rates demonstrated a relationship between cysteinate side chain rotation and activity, justifying the use of a fully dynamic model of [NiFe] metal cluster motion.
- Research Organization:
- Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
- Sponsoring Organization:
- USDOE
- DOE Contract Number:
- AC05-76RL01830
- OSTI ID:
- 1047395
- Report Number(s):
- PNNL-SA-82850; KC0304000; TRN: US201216%%254
- Journal Information:
- Journal of Chemical Theory and Computation, Vol. 8, Issue 6
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
60 APPLIED LIFE SCIENCES
COORDINATES
DATA
DENSITY
DYNAMICS
ENZYMES
FLUCTUATIONS
FUNCTIONALS
HYDROGENASES
HYDROXIDES
IONS
LIGANDS
METALS
MOTION
OXIDATION
PROTEINS
ROTATION
STABILITY
TESTING
THERMODYNAMICS
USES
lipipolysaccharide membrane
lipid bilayer
pseudomonas aeruginosa
molecular dynamics