Research Projects

Our main fields of interest are enzyme research, optopharmacology and pattern-based drug design. We focus on the following specific areas:

1. Neurelaxin: We demonstrated that non-musle myosin II (NMII) directly governs neurite growth and synapse structures, which are responsible for brain plasticity essential in learning and regeneration. In order to modulate neurite growth in vivo we developed Neurelaxin, a compound which promotes neurite growt in a minute time scale through the direct inhibition of neuronal NMII. This is a promising tool towards the development of a lead compound which improves the symptoms of neurodegenerative diseases.

The project is supported by the National Competetiveness and Excellence Program NVKP_16

2. Molecular Tattoo: We developed Molecular Tattoo, a novel tool in optopharmacology. It enables localization of drug effects at subcellular resolution in live biological objects including whole animals. Molecular Tattoo combines photoaffinity-labeling with two-photon microscopy. Precise sequential laser irradiation is used to covalently enrich low concentration photoreactive drugs on their specific targets. This results in a strong and permanent drug effect that is restricted solely to the irradiated area.

3. Mechanism of motor enzymes and force-related enzymatic processes: We have clarified the relationship between conformational changes of the lever arm, the nucleotide binding pocket and the actin binding cleft of myosin using site-specific fluorescent signals combined with transient kinetic methods. ii, We were one of the first groups to describe actin binding cleft movement in myosin induced by actin and nucleotides. iii, We solved the mechanism how different nucleotides determine the strength of actin binding by myosin, which is a key feature of the actomyosin working cycle.We also have elucidated the mechanism of coupling between the power stroke of myosin and product release steps. ii, We found that selective force perturbation predictably affects the recovery stroke of myosin.

4. Conformational transitions of enzymes: We investigate enzymatic mechanisms and related conformational transitions of several enzymes by applying different transient kinetic and fluorescence methods. We also investigate the relations of enzymatic properties and the rotational spectra of individual amino acids.

5. In silico characterisation of enzymatic processes and interactions: In collaboration with Print-Net Ltd. we developed the Drug Profile Matching (DPM) method capable to reveal the effect profiles of drugs in their entirety, and to predict uncovered effects in a systematic manner. We have also been conducting several projects in molecular dynamics of motor enzymes to simulate the effects of force perturbation.

 

Research projects

ACTOMYOSIN ATOMIC STRUCTURAL MODELS

  • weak-binding actomyosin (actin trimer docked and relaxed with up lever Dictyostelium motor domain 1VOM), extra primed state
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  • activation loop mutant weak-binding actomyosin (actin trimer docked and relaxed with 1VOM R520Q mutant)
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  • loop 3 mutant weak-binding actomyosin (actin trimer docked and relaxed with 1VOM R562Q mutant)
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  • rigor actomyosin (actin trimer docked and relaxed with down lever Dictyostelium motor domain 1Q5G)
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  • rigor actomyosin (actin trimer docked and relaxed with down lever squid motor domain 2OVK)
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