Research Topics

Loschmidt Laboratories consist of two experimental and two theoretical teams, which are collaborating tightly. Multiple rounds of computational protein design, experimental testing, and structural analyses are required for the development of novel strategies, software tools, artificial intelligence-based models, and lab-on-chips.

Zbynek Prokop’s Enzyme Kinetics and Microfluidics Team. We find answers to critical mechanistic questions related to enzyme catalysis and protein stability by kinetic analysis using advanced biophysical measurements and global data analysis. We apply these methods to a range of biomolecules important for industrial, medical and environmental biotechnologies: luciferases, haloalkane dehalogenases, fluorinases, fibroblast growth factors, thrombolytic enzymes and amyloid beta. We also develop modern microfluidics devices for high-throughput screening, combinatorial biophysical characterisation, kinetic and thermodynamic analysis of enzymes. The kinetic and thermodynamic data complement the structural and molecular modelling data to provide a detailed structure-function understanding essential for protein design and development of novel tools in protein engineering.

Martin Marek’s Structural Biology Team. We are an enthusiastic team of researchers who wish to understand the inner organisation and workings of biocatalysts. We elucidate the molecular principles and evolution of biocatalytic processes that occur in living organisms by combining molecular biology, biochemistry, X-ray crystallography and cryo-electron microscopy. The obtained structural information is complemented with kinetic measurements, theoretical calculations, and further employed in protein engineering efforts. Such complex information will contribute to the development of future, environmentally friendly technologies. Our recent achievements include delineation of the molecular basis underlying the hyperstabilisation, unravelling mechanism of coelenterazine-powered bioluminescence at alpha/beta-hydrolase fold and visualisation of the bioluminescence resonance energy transfer.

David Bednar’s Molecular Modelling and Bioinformatics Team. Our team develops new concepts, methods, and software tools for computational protein design. We apply molecular docking, molecular mechanics, molecular dynamics, quantum mechanics, and structural bioinformatics to analyse structure-function relationships. We use bacterial haloalkane dehalogenases and luciferases as the model enzymes for designing novel engineering strategies. The computational designs conducted on protein structures are materialised by site-directed mutagenesis or gene synthesis. We work in close partnership with the experimental teams, where the impact of mutations on protein structure and function are studied. We aim for rational and semi-rational engineering of biopharmaceutics for diagnostics and treatment of Alzheimer’s Disease and ischemic stroke.

Stanislav Mazurenko’s Artificial Intelligence Team. We broaden our knowledge of proteins by applying data-intensive machine learning methods to various types of protein data. We explore supervised, unsupervised, and semi-supervised approaches to decipher patterns in experimental measurements, protein sequences, structures, alignments, and computer simulations. Our goals are to gain insights into the underlying biophysical mechanisms and to create reliable and interpretable software tools for the design of improved protein variants. This is a fascinating area of research at the interface of biochemistry, biophysics, computer science, and mathematics. We leverage the data to provide all the teams with the support in making decisions, designing experiments, analysing data, and drawing conclusions.