Berlin 2024 – scientific programme

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BP: Fachverband Biologische Physik

BP 21: Poster IIIb

BP 21.25: Poster

Wednesday, March 20, 2024, 11:00–14:30, Poster C

Finding (Un)binding Pathways in Protein-Ligand Systems — •Miriam Jäger and Steffen Wolf — Biomolecular Dynamics, Institute of Physics, University of Freiburg, Hermann-Herder-Str. 3, 79104 Freiburg, Germany

Understanding dynamics and free energy landscapes of ligand association and dissociation from proteins is hampered by the slow timescales of these transitions. To enhance transition sampling we enforce ligand unbinding from a protein by applying dissipation-corrected targeted MD (dcTMD) simulations, which enforce a moving distance constraint along a pre-chosen reaction coordinate. Using a naive biasing coordinate, ligand unbinding occurs via different pathways, which need to be identified to carry out a dissipation correction. However, uncovering the different pathways along complex reaction coordinates presents a challenge. To address this challenge, we utilize the Streptavidin-biotin complex as test system. Employing various distance measures as input features to cluster similar unbinding trajectories, we aim to reconstruct unbinding pathways and connecting these pathways to internal coordinates.