Molecular Dynamics Study of Twister Ribozyme: Role of Mg2+Ions and the Hydrogen-Bonding Network in the Active Site

Zinc complexes were synthesized as catalysts that mimic the ability of carbonic anhydrase (CA) for the CO2 hydration reaction (H2O + CO2 → H+ + HCO3-). For these complexes, a tris(2-pyridylmethyl)amine (TPA) ligand mimicking only the active site, and a 6-((bis(pyridin-2-ylmethyl)amino)methyl)pyridin-2-ol (TPA-OH) ligand mimicking the hydrogen-bonding network of the secondary coordination sphere of CA were used. Potentiometric pH titration was used to determine the deprotonation ability of the Zn complexes, and their pKa values were found to be 8.0 and 6.8, respectively. Stopped-flow spectrophotometry was used to confirm the CO2 hydration rate. The rate constants were measured to be 648.4 and 730.6 M-1s-1, respectively. The low pKa value was attributed to the hydrogen-bonding network of the secondary coordination sphere of the catalyst that mimics the behavior of CA, and this was found to increase the CO2 hydration rate of the catalyst.

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Model Complexes Elucidate the Role of the Proximal Hydrogen-Bonding Network in Cytochrome P450s

Inorganic Chemistry ◽

10.1021/acs.inorgchem.0c00245 ◽

2020 ◽

Vol 59 (12) ◽

pp. 8034-8043

Author(s):

Andrew P. Hunt ◽

Subhra Samanta ◽

Matthew R. Dent ◽

Michael W. Milbauer ◽

Judith N. Burstyn ◽

...

Keyword(s):

Hydrogen Bonding ◽

Cytochrome P450s ◽

Model Complexes ◽

Hydrogen Bonding Network

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Investigation into the role of the hydrogen bonding network in cyclodextrin-based self-assembling mesophases

Journal of Materials Chemistry C ◽

10.1039/c4tc00448e ◽

2014 ◽

Vol 2 (25) ◽

pp. 4928-4936 ◽

Cited By ~ 10

Author(s):

Sandra Ward ◽

Oliver Calderon ◽

Ping Zhang ◽

Matthew Sobchuk ◽

Samantha N. Keller ◽

...

Keyword(s):

Hydrogen Bonding ◽

Self Organized ◽

Self Assembling ◽

Bond Network ◽

Hydrogen Bonding Network

The ability to form self-organized thermotropic mesophases of amphiphilic cyclodextrins correlates well with their ability to establish an intermolecular H-bond network.

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Simulating Absorption Spectra of Flavonoids in Aqueous Solution: A Polarizable QM/MM Study

Molecules ◽

10.3390/molecules25245853 ◽

2020 ◽

Vol 25 (24) ◽

pp. 5853

Author(s):

Sulejman Skoko ◽

Matteo Ambrosetti ◽

Tommaso Giovannini ◽

Chiara Cappelli

Keyword(s):

Molecular Dynamics ◽

Aqueous Solution ◽

Hydrogen Bonding ◽

Force Field ◽

Absorption Spectra ◽

Computational Study ◽

Md Simulations ◽

Quantum Mechanical ◽

Hydrogen Bonding Interactions

We present a detailed computational study of the UV/Vis spectra of four relevant flavonoids in aqueous solution, namely luteolin, kaempferol, quercetin, and myricetin. The absorption spectra are simulated by exploiting a fully polarizable quantum mechanical (QM)/molecular mechanics (MM) model, based on the fluctuating charge (FQ) force field. Such a model is coupled with configurational sampling obtained by performing classical molecular dynamics (MD) simulations. The calculated QM/FQ spectra are compared with the experiments. We show that an accurate reproduction of the UV/Vis spectra of the selected flavonoids can be obtained by appropriately taking into account the role of configurational sampling, polarization, and hydrogen bonding interactions.

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Molecular dynamics study of active-site interactions with tetracoordinate transients in acetylcholinesterase and its mutants

Biochemical Journal ◽

10.1042/bj3530645 ◽

2001 ◽

Vol 353 (3) ◽

pp. 645-653 ◽

Cited By ~ 3

Author(s):

Istvan J. ENYEDY ◽

Ildiko M. KOVACH ◽

Akos BENCSURA

Keyword(s):

Molecular Dynamics ◽

Glutamic Acid ◽

Active Site ◽

Indole Ring ◽

Active Site Residues ◽

Parallel Simulations ◽

Electrostatic Stabilization ◽

Carbenium Ion ◽

Dynamics Simulations

The role of active-site residues in the dealkylation reaction in the PSCS diastereomer of 2-(3,3-dimethylbutyl)methylphosphonofluoridate (soman)-inhibited Torpedo californicaacetylcholinesterase (AChE) was investigated by full-scale molecular dynamics simulations using CHARMM: > 400ps equilibration was followed by 150–200ps production runs with the fully solvated tetracoordinate phosphonate adduct of the wild-type, Trp84Ala and Gly199Gln mutants of AChE. Parallel simulations were carried out with the tetrahedral intermediate formed between serine-200 Oγ of AChE and acetylcholine. We found that the NεH in histidine H+-440 is positioned to protonate the oxygen in choline and thus promote its departure. In contrast, NεH in histidine H+-440 is not aligned for a favourable proton transfer to the pinacolyl O to promote dealkylation, but electrostatic stabilization by histidine H+-440 of the developing anion on the phosphonate monoester occurs. Destabilizing interactions between residues and the alkyl fragment of the inhibitor enforce methyl migration from Cβ to Cα concerted with C—O bond breaking in soman-inhibited AChE. Tryptophan-84, phenyalanine-331 and glutamic acid-199 are within 3.7–3.9 Å (1 Å=10-10 m) from a methyl group in Cβ, 4.5–5.1 Å from Cβ and 4.8–5.8 Å from Cα, and can better stabilize the developing carbenium ion on Cβ than on Cα. The Trp84Ala mutation eliminates interactions between the incipient carbenium ion and the indole ring, but also reduces its interactions with phenylalanine-331 and aspartic acid-72. Tyrosine-130 promotes dealkylation by interacting with the indole ring of tryptophan-84. Glutamic acid-443 can influence the orientation of active-site residues through tyrosine-421, tyrosine-442 and histidine-440 in soman-inhibited AChE, and thus facilitate dealkylation.

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