About the Talk
Presenter
Tandaç Furkan Güçlü: Post-Doctoral Research Associate, Sabancı University
Tandaç Furkan Güçlü earned his PhD in Molecular Biology, Genetics and Bioengineering from Sabancı University in 2021 and has been a postdoctoral researcher in the MIDST lab since then, where he works on the EuroCC4SEE project. He employs molecular dynamics, GPU-accelerated free energy perturbation and network-theoretic analyses to map how point mutations affect protein structure and ligand binding. His work has led to publications on alchemical screening of dihydrofolate reductase and allosteric network mapping in PDZ domains, and he develops scalable HPC workflows and training programmes for computational structural biology.
Abstract
Antibiotic resistance poses a pressing challenge for global health as bacterial mutations undermine drug efficacy. Here we introduce a high-throughput computational pipeline that harnesses alchemical free energy perturbation simulations on GPU-based high-performance clusters to quantify the impact of single amino acid mutations on dihydrofolate reductase binding to trimethoprim and its 4′-deoxy derivative. We selected 33 key positions informed by experimental and structural studies and performed 4,752 simulations across apo, trimethoprim-bound, and 4′-deoxy trimethoprim-bound forms. Results reveal mutation-specific shifts in relative binding free energy within 1 kcal/mol of experimental values and identify hotspots that preferentially favor derivative binding. This approach enables systematic, scalable evaluation of mutational effects with precision relevant to drug resistance research.
Date: May 27th, 2025 – 3:00 pm (GMT+3)
Language: English