Using Molecular Simulation to Study Biocatalysis in Ionic Liquids

Sprenger, Kayla G.; Pfaendtner, Jim

doi:10.1016/bs.mie.2016.05.020

Cited by 13 publications

(6 citation statements)

References 76 publications

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“…Packmol was used to generate cubic simulation boxes of ∼8.8 nm length with ∼65 000 atoms. On the basis of our previous work, , the IL was modeled using the general AMBER force field (GAFF) with point charges determined via the RESP calculation method and scaled down by 20% to improve the simulated dynamical properties of the IL . The TIP3P water model was used to represent water, and the Amber14SB force field was used to model both the E1 enzyme and sodium ions that were added to each system to achieve overall charge neutrality.…”

Section: Methodsmentioning

confidence: 99%

Mechanism of Competitive Inhibition and Destabilization of Acidothermus cellulolyticus Endoglucanase 1 by Ionic Liquids

et al. 2017

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The ability of ionic liquids (ILs) to solubilize cellulose has sparked interest in their use for enzymatic biomass processing. However, this potential is yet to be realized, primarily because ILs inactivate requisite cellulases by mechanisms that are yet to be identified. We used a combination of enzymology, circular dichroism (CD), nuclear magnetic resonance (NMR), and molecular dynamics (MD) methods to investigate the molecular basis for the inactivation of the endocellulase 1 (E1) from Acidothermus cellulolyticus by the imidazolium IL 1-butyl-3-methylimidazolium chloride ([BMIM][Cl]). Enzymatic studies revealed that [BMIM][Cl] inactivates E1 in a biphasic manner that involves rapid, reversible inhibition, followed by slow, irreversible deactivation. Backbone NMR signals of the 40.5 kDa E1 were assigned by triple resonance NMR methods, enabling monitoring of residue-specific perturbations. H-N NMR titration experiments revealed that [BMIM][Cl] binds reversibly to the E1 active site, indicating that reversible deactivation is due to competitive inhibition of substrate binding. Prolonged incubation with [BMIM][Cl] led to substantial global changes in the H-N heteronuclear single quantum coherence NMR and CD spectra of E1 indicative of protein denaturation. Notably, weak interactions between [BMIM][Cl] and residues at the termini of several helices were also observed, which, together with MD simulations, suggest that E1 denaturation is promoted by [BMIM][Cl]-induced destabilization of helix capping structures. In addition to identifying determinants of E1 inactivation, our findings establish a molecular framework for engineering cellulases with improved IL compatibility.

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Section: Methodsmentioning

confidence: 99%

Mechanism of Competitive Inhibition and Destabilization of Acidothermus cellulolyticus Endoglucanase 1 by Ionic Liquids

et al. 2017

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“…Recent progress in analytical studies of ILs using NMR, ,− mass spectrometry, − thermal techniques, − theoretical modeling, ,,,− and other analytical approaches − has revealed an important mechanistic picture. As expected, ILs fully realize the potential of tunable interactions at the molecular level, as discussed above (Figure ).…”

Section: Introductionmentioning

confidence: 99%

Biological Activity of Ionic Liquids and Their Application in Pharmaceutics and Medicine

2017

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Ionic liquids are remarkable chemical compounds, which find applications in many areas of modern science. Because of their highly tunable nature and exceptional properties, ionic liquids have become essential players in the fields of synthesis and catalysis, extraction, electrochemistry, analytics, biotechnology, etc. Apart from physical and chemical features of ionic liquids, their high biological activity has been attracting significant attention from biochemists, ecologists, and medical scientists. This Review is dedicated to biological activities of ionic liquids, with a special emphasis on their potential employment in pharmaceutics and medicine. The accumulated data on the biological activity of ionic liquids, including their antimicrobial and cytotoxic properties, are discussed in view of possible applications in drug synthesis and drug delivery systems. Dedicated attention is given to a novel active pharmaceutical ingredient-ionic liquid (API-IL) concept, which suggests using traditional drugs in the form of ionic liquid species. The main aim of this Review is to attract a broad audience of chemical, biological, and medical scientists to study advantages of ionic liquid pharmaceutics. Overall, the discussed data highlight the importance of the research direction defined as "Ioliomics", studies of ions in liquids in modern chemistry, biology, and medicine.

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“…The IL tolerance of several different enzymes, including xylanase, lipase, chymotrypsin, and several cellulases, has been studied by MD simulations and with various experimental techniques. − Specific interactions between cations, anions, and the proteins of interest were analyzed to determine why certain ILs stabilize or destabilize these enzymes. Typically, the analysis of IL–protein MD simulations includes many standard measures of protein or solvent structure and dynamics including root-mean-square deviation and fluctuation (RMSD and RMSF) of protein structure, principle component analysis (PCA), interaction lifetimes between ions and catalytic residues, surface residue entropy, structuring of water and ions around the protein, and secondary structure evolution, among others . Frequently, proteins remain very close to their crystallographic structures during molecular dynamics simulations even when they are solvated in very high concentrations (50% w/w or more) of IL mixed with water.…”

Section: Introductionmentioning

confidence: 99%

“…Typically, the analysis of IL− protein MD simulations includes many standard measures of protein or solvent structure and dynamics including root-meansquare deviation and fluctuation (RMSD and RMSF) of protein structure, principle component analysis (PCA), interaction lifetimes between ions and catalytic residues, surface residue entropy, structuring of water and ions around the protein, and secondary structure evolution, among others. 23 Frequently, proteins remain very close to their crystallographic structures during molecular dynamics simulations even when they are solvated in very high concentrations (50% w/w or more) of IL mixed with water. It often takes hundreds of nanoseconds or more to observe significant structural changes beyond thermal fluctuations at these concentrations, even when it is known experimentally that the protein unfolds quite readily in ILs.…”

Section: ■ Introductionmentioning

confidence: 99%

Destabilization of Human Serum Albumin by Ionic Liquids Studied Using Enhanced Molecular Dynamics Simulations

Jaeger

Pfaendtner

2016

J. Phys. Chem. B

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Ionic liquid (IL) containing solvents can change the structure, dynamics, function, and stability of proteins. In order to investigate the mechanisms by which ILs induce structural changes in a large multidomain protein, we study the interactions of human serum albumin (HSA) with two different ILs, 1-butyl-3-methylimidazolium tetrafluoroborate and choline dihydrogen phosphate. Root mean square deviation and fluctuation calculations indicate that high concentrations of ILs in mixtures with water lead to protein structures that remain close to their crystallographic structures on time scales of hundreds of nanoseconds. To overcome potential time scale limitations due to the high viscosity of the solvent, we employed enhanced sampling techniques to estimate the free energy of an experimentally determined important transition within the protein structure. Metadynamics simulations show that the free energy landscape of the unfolding of loop 1 of domain I is different in the presence of ILs than it is in water, consistent with previously published experimental evidence. We then apply essential dynamics coarse graining to systematically predict differences in the dynamics of proteins solvated in IL-water mixtures versus pure water systems. We also demonstrate that the presence of ionic liquids changes the distribution of intermolecular distances among several ligands, indicating that the protein structure swells in the presence of certain ILs, consistent with experimental evidence.

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Using Molecular Simulation to Study Biocatalysis in Ionic Liquids

Cited by 13 publications

References 76 publications

Mechanism of Competitive Inhibition and Destabilization of Acidothermus cellulolyticus Endoglucanase 1 by Ionic Liquids

Mechanism of Competitive Inhibition and Destabilization of Acidothermus cellulolyticus Endoglucanase 1 by Ionic Liquids

Biological Activity of Ionic Liquids and Their Application in Pharmaceutics and Medicine

Destabilization of Human Serum Albumin by Ionic Liquids Studied Using Enhanced Molecular Dynamics Simulations

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