Investigation of Rare Protein Conformational Transitions via Dissipation-Corrected Targeted Molecular Dynamics

Learning Protein–Ligand Unbinding Pathways via Single-Parameter Community Detection

“…To address this challenge, we recently developed two strategies. In principle, given sufficient sampling, a high dimensional model in the CV space can be constructed . However, given the sampling limitations imposed by the computational cost of fully atomistic MD simulations that are necessary for this approach, we find it more practical to work with a one-dimensional model for protein–ligand complexes instead.…”

“…For the prediction of both binding and unbinding rates, our group has developed dissipation-corrected targeted Molecular Dynamics (dcTMD), , which allows estimating free energies Δ G and friction factors Γ from fully atomistic MD simulations with constant velocity constraints. These fields are employed in a numerical integration of a Langevin equation, which are a popular approach to coarse-grain dynamics, , to effectively sample (un)­binding processes and infer their time scales .…”