An official website of the United States government
FTIR spectroscopy accompanied by quantum chemical simulations can reveal important information about molecular structure and intermolecular interactions in the condensed phase. Simulations typically account for the solvent either through cluster quantum mechanical (QM) models, polarizable continuum models (PCM), or hybrid quantum mechanical/molecular mechanical (QM/MM) models. Recently, we studied the effect of aqueous solvent interactions on the vibrational frequencies of lumiflavin, a minimal flavin model, using cluster QM and PCM models. Those models successfully reproduced the relative frequencies of four prominent stretching modes of flavin’s isoalloxazine ring in the diagnostic 1450–1750 cm−1 range but poorly reproduced the relative band intensities. Here, we extend our studies on this system and account for solvation through a series of increasingly sophisticated models. Only by combining elements of QM clusters, QM/MM, and PCM approaches do we obtain an improved agreement with the experiment. The study sheds light more generally on factors that can impact the computed frequencies and intensities of IR bands in solution.
more »
« less
The influence of model building schemes and molecular dynamics sampling on QM-cluster models: the chorismate mutase case study
Most QM-cluster models of enzymes are constructed based on X-ray crystal structures, which limits comparison toin vivostructure and mechanism. This work introduces an MD to QM-cluster model workflow.
more »
« less
- Award ID(s):
- 1846408
- PAR ID:
- 10529639
- Publisher / Repository:
- Royal Society of Chemistry
- Date Published:
- Journal Name:
- Physical Chemistry Chemical Physics
- Volume:
- 26
- Issue:
- 16
- ISSN:
- 1463-9076
- Page Range / eLocation ID:
- 12467 to 12482
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
We have designed a [Fe(SH)4H]− model with the fifth proton binding either to Fe or S. We show that the energy difference between these two isomers (∆E) is hard to estimate with quantum-mechanical (QM) methods. For example, different density functional theory (DFT) methods give ∆E estimates that vary by almost 140 kJ/mol, mainly depending on the amount of exact Hartree–Fock included (0%–54%). The model is so small that it can be treated by many high-level QM methods, including coupled-cluster (CC) and multiconfigurational perturbation theory approaches. With extrapolated CC series (up to fully connected coupled-cluster calculations with singles, doubles, and triples) and semistochastic heat-bath configuration interaction methods, we obtain results that seem to be converged to full configuration interaction results within 5 kJ/mol. Our best result for ∆E is 101 kJ/mol. With this reference, we show that M06 and B3LYP-D3 give the best results among 35 DFT methods tested for this system. Brueckner doubles coupled cluster with perturbaitve triples seems to be the most accurate coupled-cluster approach with approximate triples. CCSD(T) with Kohn–Sham orbitals gives results within 4–11 kJ/mol of the extrapolated CC results, depending on the DFT method. Single-reference CC calculations seem to be reasonably accurate (giving an error of ∼5 kJ/mol compared to multireference methods), even if the D1 diagnostic is quite high (0.25) for one of the two isomers.more » « less
-
Glycoside hydrolase enzymes are important for hydrolyzing the β-1,4 glycosidic bond in polysaccharides for deconstruction of carbohydrates. The two-step retaining reaction mechanism of Glycoside Hydrolase Family 7 (GH7) was explored with different sized QM-cluster models built by the Residue Interaction Network ResidUe Selector (RINRUS) software using both the wild-type protein and its E217Q mutant. The first step is the glycosylation, in which the acidic residue 217 donates a proton to the glycosidic oxygen leading to bond cleavage. In the subsequent deglycosylation step, one water molecule migrates into the active site and attacks the anomeric carbon. Residue interaction-based QM-cluster models lead to reliable structural and energetic results for proposed glycoside hydrolase mechanisms. The free energies of activation for glycosylation in the largest QM-cluster models were predicted to be 19.5 and 31.4 kcal mol −1 for the wild-type protein and its E217Q mutant, which agree with experimental trends that mutation of the acidic residue Glu217 to Gln will slow down the reaction; and are higher in free energy than the deglycosylation transition states (13.8 and 25.5 kcal mol −1 for the wild-type protein and its mutant, respectively). For the mutated protein, glycosylation led to a low-energy product. This thermodynamic sink may correspond to the intermediate state which was isolated in the X-ray crystal structure. Hence, the glycosylation is validated to be the rate-limiting step in both the wild-type and mutated enzyme.more » « less
-
Abstract This study investigates dioxygen binding and 2‐oxoglutarate (2OG) coordination by two model non‐heme FeII/2OG enzymes: a class 7 histone demethylase (PHF8) that catalyzes the hydroxylation of its H3K9me2 histone substrate leading to demethylation reactivity and the ethylene‐forming enzyme (EFE), which catalyzes two competing reactions of ethylene generation and substratel‐Arg hydroxylation. Although both enzymes initially bind 2OG by using anoff‐line2OG coordination mode, in PHF8, the substrate oxidation requires a transition to anin‐linemode, whereas EFE is catalytically productive for ethylene production from 2OG in theoff‐linemode. We used classical molecular dynamics (MD), quantum mechanics/molecular mechanics (QM/MM) MD and QM/MM metadynamics (QM/MM‐MetD) simulations to reveal that it is the dioxygen binding process and, ultimately, the protein environment that control the formation of thein‐lineFeIII‐OO⋅−intermediate in PHF8 and theoff‐lineFeIII‐OO⋅−intermediate in EFE.more » « less
-
This work is devoted to deriving and implementing analytic second- and third-order energy derivatives with respect to the nuclear coordinates and external electric field within the framework of the hybrid quantum mechanics/molecular mechanics method with induced charges and dipoles (QM/DIM). Using these analytic energy derivatives, one can efficiently compute the harmonic vibrational frequencies, infrared (IR) and Raman scattering (RS) spectra of the molecule in the proximity of noble metal clusters/nanoparticles. The validity and accuracy of these analytic implementations are demonstrated by the comparison of results obtained by the finite-difference method and the analytic approaches and by the full QM and QM/DIM calculations. The complexes formed by pyridine and two sizes of gold clusters (Au18 and Au32) at varying intersystem distances of 3, 4, and 5 Å are used as the test systems, and Raman spectra of 4,4′-bipyridine in the proximity of Au2057 and Ag2057 metal nanoparticles (MNP) are calculated by the QM/DIM method and compared with experimental results as well. We find that the QM/DIM model can well reproduce the IR spectra obtained from full QM calculations for all the configurations, while although it properly enhances some of the vibrational modes, it artificially overestimates RS spectral intensities of several modes for the systems with very short intersystem distance. We show that this could be improved, however, by incorporating the hyperpolarizability of the gold metal cluster in the evaluation of RS intensities. Additionally, we address the potential impact of charge migration between the adsorbate and MNPs.more » « less
- Free Publicly Accessible Full Text
-
Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1039/D3CP06100K
