ESR4: Özge Ergun
Curutchet Research Group
Computational Photobiology Lab
University of Barcelona
Prof. Carles Curutchet
Excitation energy transfer applied to drug design
The Förster resonance energy transfer (FRET) technique is an important tool in structural biology, due to its ability to monitor and measure distances in biological systems. Albeit FRET is widely used to measure distances in fluorophore-tagged proteins, intrinsic FRET processes in protein-ligand complexes prevent straightforward application of Förster theory due to the lack of rotational freedom of the Trp and ligands involved and their relatively short separations. In this project, we will investigate the application of a novel multiscale computational methodology to characterize FRET data in protein-ligand complexes based on advanced polarizable quantum/molecular mechanical (QM/MM) calculations. The approach will combine Molecular Dynamics simulations which advanced methods for the calculation of FRET couplings (based on transition densities and charges), which overcome Förster dipole approximation and allow to account for modulation of FRET couplings by the heterogeneous polarizable properties of the environment. This strategy will be applied to characterize allosteric binding sites and ligand binding modes.
The main objectives of the project are as follows:
1) Develop a computational tool to generate FRET observables from MD trajectories.
2) Select a library of promiscuous fragments with tailored FRET properties.
3) Assess the ability of FRET simulations to characterize allosteric binding sites and ligand binding modes for drug discovery targets.
Brief Scientific Bio
I obtained my Bachelor’s Degree from Bogazici University (Turkey). During these studies, I took a computational chemistry course that was a milestone in my career, and I worked on a computational chemistry project about the selectivity in Diels-Alder reactions and spent one semester at Ghent University (Belgium) on Erasmus.
After my graduation, I completed an internship at Vrije Universiteit Brussel (Belgium) focused on computational studies of chalcogen & tetrel bonds of linear molecules, a project that led to an article published in 2021 of which I am a co-author.
Afterwards, I completed my Master’s Degree at KU Leuven (Belgium), which included an internship at Solvay (Belgium) where I worked on finding dielectric properties of polymers by using Molecular Dynamics. My master thesis addressed artificial enzymes and, besides improving my computational chemistry skills, gave me the chance to dive deeper into the world of biochemistry and inorganic chemistry.
In April 2022, I joined Prof. Carles Curutchet’s lab at University of Barcelona (Spain), where I’m pursuing a PhD project focused on the structural characterization of allosteric binding sites with a combination of FRET spectroscopic measurements and multiscale simulations.