<scp>CHARMM</scp>: A program for macromolecular energy, minimization, and dynamics calculations

Brooks, Bernard R.; Bruccoleri, Robert E.; Olafson, Barry D.; States, David J.; Swaminathan, S.; Karplus, Martin

doi:10.1002/jcc.540040211

Cited by 14,667 publications

(12,864 citation statements)

References 72 publications

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“…Minimized structures generated in this way after different equilibration times at 300 K (and thus from different room temperature structures) were virtually identical. The molecular dynamics and energy minimizations were performed using version 27 of CHARMM (20).…”

Section: Methodsmentioning

confidence: 99%

NO Binding and Dynamics in Reduced Heme−Copper Oxidases aa₃ from Paracoccus denitrificans and ba₃ from Thermus thermophilus

et al. 2004

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Cytochrome c oxidase (CcO) has a high affinity for nitric oxide (NO), a property involved in the regulation of respiration. It has been shown that the recombination kinetics of photolyzed NO with reduced CcO from Paracoccus denitrificans on the picosecond time scale depend strongly on the NO/ enzyme stoichiometry and inferred that more than one NO can be accommodated by the active site, already at mildly suprastoichiometric NO concentrations. We have largely extended these studies by monitoring rebinding dynamics from the picosecond to the microsecond time scale, by performing parallel steadystate low-temperature electron paramagnetic resonance (EPR) characterizations on samples prepared similarly as for the optical experiments and comparing them with molecular-modeling results. A comparative study was performed on CcO ba 3 from Thermus thermophilus, where two NO molecules cannot be copresent in the active site in the steady state because of its NO reductase activity. The kinetic results allow discrimination between different models of NO-dependent recombination and show that the overall NO escape probability out of the protein is high when only one NO is bound to CcO aa 3 , whereas strong rebinding on the 15-ns time scale was observed for CcO ba 3 . The EPR characterizations show similar results for aa 3 at substoichiometric NO/enzyme ratios and for ba 3 , indicating formation of a 6-coordinate heme-NO complex. The presence of a second NO molecule in the aa 3 active site strongly modifies the heme-NO EPR spectrum and can be rationalized by a rotation of the Fe-N-O plane with respect to the histidine that coordinates the heme iron. This proposal is supported by molecular-modeling studies that indicate a ∼63°rotation of heme-bound NO upon binding of a second NO to the close-lying copper center CuB. It is argued that the second NO binds to CuB.

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Section: Methodsmentioning

confidence: 99%

NO Binding and Dynamics in Reduced Heme−Copper Oxidases aa₃ from Paracoccus denitrificans and ba₃ from Thermus thermophilus

et al. 2004

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“…The protein structure file of the entire system was generated with CHARMM (28). Minimization and molecular dynamics (MD) simulations were carried out with CHARMM27 parameters (28,29) using NAMD (30), due to its demonstrated excellent performance in parallel environments. Periodic boundary conditions and a dielectric constant of 1 were used throughout the simulations.…”

Section: Methodsmentioning

confidence: 99%

Molecular Dissection of a Critical Specificity Determinant within the Amino Acid Editing Domain of Leucyl-tRNA Synthetase

et al. 2003

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A highly conserved threonine residue marks the amino acid binding pocket within the editing active site of leucyl-tRNA synthetases (LeuRSs). It is essential to substrate specificity for the Escherichia coli enzyme in that it blocks the cognate leucine amino acid from binding in the hydrolytic editing active site. We combined mutagenesis and computational approaches to elucidate the molecular role of the critical side chain of this threonine residue. Removal of the terminal methyl group of the threonine side chain by replacement with serine yielded a mutant LeuRS that hydrolyzes Leu-tRNA Leu . Substitution of valine for the conserved threonine conferred similar activities to the wild-type enzyme. However, an additional substitution within the editing active site suggested synergistic interactions with the conserved threonine site that significantly affected amino acid editing. On the basis of our combined biochemical and computational data, we propose that the threonine 252 side chain not only sterically hinders the cognate charged leucine from binding for hydrolysis but also plays a critical role in maintaining an active site geometry that is required for the fidelity of LeuRS.

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“…Standard uncertainties (±1σ) were determined from the total average and those from the 10 separate blocks. All simulations employed the CHARMM program 49 and all path-integral simulations used a parallel version that efficiently distributes integral calculations for the quantized beads.…”

Section: Simulation Detailsmentioning

confidence: 99%

Combined QM/MM and path integral simulations of kinetic isotope effects in the proton transfer reaction between nitroethane and acetate ion in water

2007

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An integrated Feynman path integral-free energy perturbation and umbrella sampling (PI-FEP/UM) method has been used to investigate the kinetic isotope effects (KIEs) in the proton transfer reaction between nitroethane and acetate ion in water. In the present study, both nuclear and electronic quantum effects are explicitly treated for the reacting system. The nuclear quantum effects are represented by bisection sampling centroid path integral simulations, while the potential energy surface is described by a combined quantum mechanical and molecular mechanical (QM/MM) potential. The accuracy essential for computing KIEs is achieved by a FEP technique that transforms the mass of a light isotope into a heavy one, which is equivalent to the perturbation of the coordinates for the path integral quasiparticle in the bisection sampling scheme. The PI-FEP/UM method is applied to the proton abstraction of nitroethane by acetate ion in water through molecular dynamics simulations. The rule of the geometric mean and the Swain-Schaad exponents for various isotopic substitutions at the primary and secondary sites have been examined. The computed total deuterium KIEs are in accord with experiments. It is found that the mixed isotopic Swain-Schaad exponents are very close to the semiclassical limits, suggesting that tunneling effects do not significantly affect this property for the reaction between nitroethane and acetate ion in aqueous solution.

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CHARMM: A program for macromolecular energy, minimization, and dynamics calculations

Cited by 14,667 publications

References 72 publications

NO Binding and Dynamics in Reduced Heme−Copper Oxidases aa₃ from Paracoccus denitrificans and ba₃ from Thermus thermophilus

NO Binding and Dynamics in Reduced Heme−Copper Oxidases aa₃ from Paracoccus denitrificans and ba₃ from Thermus thermophilus

Molecular Dissection of a Critical Specificity Determinant within the Amino Acid Editing Domain of Leucyl-tRNA Synthetase

Combined QM/MM and path integral simulations of kinetic isotope effects in the proton transfer reaction between nitroethane and acetate ion in water

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CHARMM: A program for macromolecular energy, minimization, and dynamics calculations

Cited by 14,667 publications

References 72 publications

NO Binding and Dynamics in Reduced Heme−Copper Oxidases aa3 from Paracoccus denitrificans and ba3 from Thermus thermophilus

NO Binding and Dynamics in Reduced Heme−Copper Oxidases aa3 from Paracoccus denitrificans and ba3 from Thermus thermophilus

Molecular Dissection of a Critical Specificity Determinant within the Amino Acid Editing Domain of Leucyl-tRNA Synthetase

Combined QM/MM and path integral simulations of kinetic isotope effects in the proton transfer reaction between nitroethane and acetate ion in water

Contact Info

Product

Resources

About

NO Binding and Dynamics in Reduced Heme−Copper Oxidases aa₃ from Paracoccus denitrificans and ba₃ from Thermus thermophilus

NO Binding and Dynamics in Reduced Heme−Copper Oxidases aa₃ from Paracoccus denitrificans and ba₃ from Thermus thermophilus