Data-integrated simulation of enzymes

PN 3-6

Project description

An integrated simulation approach will be developed and applied to model biochemical and biophysical properties of enzymes in aqueous and non-aqueous solvents: solubility and enzymatic function. We will tackle three major challenges: (i) Modelling of the thermodynamics of complex mixtures of substrates, products, additives, and solvents. (ii) Modelling of substrate binding to the enzyme, identification of bottlenecks and binding sites, and design of improved enzyme variants. (iii) Bridging the scale between microscopic (molecular) modelling and macroscopic kinetic models to interpret experimental data. The goal of the project is to establish a holistic modelling strategy, which enables the design of biocatalytic systems from first principles.

Project information

Project title Data-integrated simulation of enzymes
Project leaders Jürgen Pleiss (Niels Hansen)
Project duration January 2019 - June 2021
Project number PN 3-6

Publications PN 3-6

  1. 2024

    1. H. F. Carvalho, L. Mestrom, U. Hanefeld, and J. Pleiss, “Beyond the Chemical Step: The Role of Substrate Access in Acyltransferase from Mycobacterium smegmatis,” ACS Catal., vol. 14, pp. 10077–10088, Jun. 2024, doi: 10.1021/acscatal.4c00812.

  2. 2022

    1. M. Gültig, J. P. Range, B. Schmitz, and J. Pleiss, “Integration of Simulated and Experimentally Determined Thermophysical Properties of Aqueous Mixtures by ThermoML,” Journal of Chemical & Engineering Data, vol. 67, Art. no. 11, 2022, doi: 10.1021/acs.jced.2c00391.

  3. 2021

    1. H. Carvalho, V. Ferrario, and J. Pleiss, “The molecular mechanism of methanol inhibition in CALB-catalyzed alcoholysis: analyzing molecular dynamics simulations by a Markov state model,” J Chem Theory Comput, vol. 17, pp. 6570–6582, 2021, doi: https://doi.org/10.1021/acs.jctc.1c00559.

  4. 2020

    1. X. Xu, J. Range, G. Gygli, and J. Pleiss, “Analysis of Thermophysical Properties of Deep Eutectic Solvents by Data Integration,” Journal of Chemical & Engineering Data, vol. 65, pp. 1172–1179, 2020, doi: https://doi.org/10.1021/acs.jced.9b00555.
    2. G. Gygli, X. Xu, and J. Pleiss, “Meta-analysis of viscosity of aqueous deep eutectic solvents and their components,” Scientific Reports, vol. 10, p. 21395, 2020.

  5. 2019

    1. R. Roddan et al., “The acceptance and kinetic resolution of alpha-methyl substituted aldehydes by norcoclaurine synthases.,” ACS Catalysis, vol. 9, pp. 9640–9649, 2019.
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