(376as) Modeling Inhibition of Biocatalysts By Ionic Liquids Using Metadynamics
- Conference: AIChE Annual Meeting
- Year: 2019
- Proceeding: 2019 AIChE Annual Meeting
- Group: Computational Molecular Science and Engineering Forum
- Time: Tuesday, November 12, 2019 - 3:30pm-5:00pm
To this end, we will present our work on a model system: a retaining cellulase (endocellulase 1) in complex with a cellotetraose molecule, solvated at varying concentrations of an aqueous IL (1-butyl-3-methylimidazolium chloride) solution. Preliminary results indicate that preferential solvation of cellulose in ionic liquids, and inhibition of important binding site residues by cations may result in a decreased affinity between cellulose cellulase binding. To overcome the time-scale limitations of classical simulations and further understand the energetic driving forces of these interactions, we have implemented the funnel metadynamics variant to increase sampling of ligand binding and unbinding events. To this end, we hope to gain a better molecular understanding of how protein-solvent, ligand-solvent, and protein-ligand interactions are impacted in the presence of ILs.
 V. Jaeger, P. Burney, J. Pfaendtner, âComparison of Three Ionic Liquid-Tolerant Cellulases by Molecular Dynamicsâ, Biophys. J., 2015, 108(4) 880â892.
 P. Engel, R. Mladenov, H. Wulfhorst, G. Jager, & A. C. Spiess. âPoint by point analysis: how ionic liquid affects the enzymatic hydrolysis of native and modified celluloseâ, Green Chem., 2013, 12, 1959-1966.
 Wilkes, J. S. âProperties of ionic liquid solvents for catalysisâ, J. Mol. Catal. A, 2004, 11-17, 1381-1169.
V. Limongelli, M. Bonomi, M. Parrinello, "Funnel Metadynamics as accurate binding free-energy method", PNAS, 2013, 110 (16) 6358-6363