Presentation Title
A quantum leap of understanding protein structure dynamics to function correlation by Single molecule studies and machine learning analysis
Presentation Abstract
Single molecule studies have revolutionized our understanding of biomolecular recognition and have provided direct evidence of the intricate correlation of conformational dynamics, spatial localization and functional output. smFRET and single particle tracking have become a mainstream technique for studying biomolecular structural dynamics and spatial localization. The inherently complex behavior of biological systems can vary drastically both in time and across systems, consequently imposing considerable analytical challenges.
We have developed tools based on machine learning for the rapid and automated analysis, processing and data classification of smFRET and single particle tracking data. Implementation of machine learning analysis allows for acceleration of data treatment by a few orders of magnitude without a priori knowledge of the systems while at the same time is free of potential cognitive biases. Based on this sophisticated analysis we have introduced the concept of Biased metabolism of metabolic enzymes, the mechanism of CRISPR-Cas12a and how motions undelries the functionality of metabolic enzymes
Relevant publications of my group
- Stella, S. et al. Conformational Activation Promotes CRISPR-Cas12a Catalysis and Resetting of the Endonuclease Activity. Cell 2018, 175, 1856-1871.e1821.
- Jensen, S. B. et al. Biased cytochrome P450-mediated metabolism via small-molecule ligands binding P450 oxidoreductase. Nat. Commun. 2021, 12, 2260.
- Pinholt, H. D. et al. Single-particle diffusional fingerprinting: A machine-learning framework for quantitative analysis of heterogeneous diffusion. Proceedings of the National Academy of Sciences 2021, 118, e2104624118.
- Malle, M. G. et al. Single-particle combinatorial multiplexed liposome fusion mediated by DNA. Nat. Chem. 2022.
- Schmidt, S. G. et al. The dopamine transporter antiports potassium to increase the uptake of dopamine. Nat. Commun. 2022, 13, 2446.
About Nikos
Nikos Hatzakis’ main research interest is to obtain a fundamental understanding of the parameters underlying regulation of enzymatic function. Enzymes regulate a plethora of vital cellular processes and aberration in their function can result in countless disease states. They are also essential components in multiple industrial applications including drug synthesis and detergent development. Harnessing the biomolecular insights of current single molecule experiments allows us to unmask the structural and functional dynamics of major drug metabolism enzymes. Understanding how these enzymes operate paves the way for the design of novel pharmaceutics.
