This project will use GPU-accelerated molecular modelling and molecular dynamics simulations to study protein–DNA interactions and DNA-containing biomolecular systems relevant to biosensor-oriented molecular design. The work is connected to ongoing research in computational chemistry, structural biophysics, and the European iSenseDNA project at Uppsala University. The project will focus on three related classes of systems. First, TopR1–DNA complexes will be simulated to investigate DNA recognition, DNA bending, catalytic-site organization, and the structural consequences of selected TopR1 variants. Second, additional protein–DNA and aptamer-related complexes will be modelled to study conformational dynamics, molecular recognition, and stability of nucleic-acid/protein interfaces. Third, coarse-grained DNA simulations will be used when appropriate to explore larger-scale DNA conformational behaviour that is difficult to sample with atomistic simulations alone. The computational workflow will combine atomistic molecular dynamics, mainly with GROMACS, with coarse-grained DNA modelling using oxDNA when suitable. For selected systems, multiple independent replicas will be used to assess reproducibility and distinguish stable structural features from trajectory-specific fluctuations. Enhanced sampling or restrained simulation protocols may also be applied when standard molecular dynamics is not sufficient to explore relevant conformational transitions. The requested Arrhenius GPU allocation will allow efficient execution of production molecular dynamics, benchmark tests on the GH200 architecture, and systematic comparison of variants, controls, and alternative starting conformations. The simulations will provide molecular-level information on protein–DNA recognition, variant-dependent stability, DNA deformation, and structure–function relationships relevant to DNA-based sensing and biomolecular engineering. This project belongs to the Department of Chemistry – BMC, Chemistry for Life Sciences, Uppsala University.