Research Objectives and Methods
In close cooperation with the Institute for Biological Interfaces (IBG-1) compartmentalised Nano-Micro-Bioreactors are studied by theory and experiment. The goal of the cooperation between IBG-1 and IMVT is the development of a novel class of bioreactors that contain biocatalysts arranged in compartments of both nanometer and micrometer-scaled dimensions.
Enzyme-modified DNA origami structures, which function as supramolecular biocatalytic entities (SBE) that can be immobilised on micrometer-sized beads as solid supports in a packed-bed microfluidic reactor, will be designed and synthesised by IBG-1. These novel SBE-based micro flow reactor systems shall be studied in the proposed doctoral research in detail by modelling and simulation, mainly based on the use of particle-based simulation methods. This involves in a first stage the analysis of intrinsic enzyme reaction kinetics and potential mass transport limitations based on experimental data provided by IBG-1 using MATLAB as well as reactor simulations with computational fluid dynamics tools such as ANSYS FLUENT. Further, the DNA origami nanoplates have to be mapped for in-silico implementation in the open source Brownian dynamics (BD) software GeomBD. Molecular structures and relevant force fields have to be either calculated, e.g., using the AMBER open source software package or obtained from protein databanks. Parametric studies have to be performed with GeomBD using high-performance computing infrastructure at SCC with the aim of establishing structure-activity-relationships between experimental rate constants and BD kinetic parameters of enzyme-substrate complexes by means of state of the art multivariate data analysis techniques.
Close cooperation with the experimentalists at IBG-1 is planned. The long-term goal of the cooperation is to establish an integrated system where model-based simulation allows to predict the outcome of the stereoselective reduction occurring on the SBE.
Requirements: Chemical engineering background, excellent computational skills and deep interest in numerical simulation, good or at least basic understanding of molecular chemistry and biocatalysis