Regensburg 2022 – scientific programme

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BP: Fachverband Biologische Physik

BP 7: Poster 1

BP 7.24: Poster

Monday, September 5, 2022, 18:00–20:00, P1

Finding protein-ligand unbinding pathways in dcTMD simulations using distance-based clustering — •Victor Tänzel — Institute of Physics, Albert Ludwigs University, Freiburg, Germany

The exploration of protein-ligand dynamics by fully atomic simulations is of immense interest, for example in drug design, yet remains unfeasible in unbiased molecular dynamics (MD). To trigger rare events, we employ dissipation-corrected targeted MD (dcTMD) simulations, in which a moving distance constraint biases a prechosen reaction coordinate x, here the protein-ligand distance. The method combines a Markovian Langevin equation with a second-order cumulant expansion of the Jarzynski equality. From the required constraint forces, a free energy profile Δ G(x) as well as a friction coefficient Γ(x) are extracted.

Transitions often occur along multiple pathways. In order to find these pathways, we study distance-based clustering approaches combining a pairwise ligand RMSD with the Leiden community detection algorithm. Here, we demonstrate the capabilities of this approach with the example of the A2A-ZMA complex and estimate (un-)binding rates.