02.05.23 - Samuel Rudge & Miriam Jäger

 

 

 

 

 

 

 

 

Pathways in Protein-Ligand Systems
Applying dissipation-corrected Targeted Molecular Dynamics Simulations to Protein Ligand Systems
 

The understanding of dynamics and free energy landscapes of ligand association and dissociation from proteins is limited by the timescales of these transitions. We used dissipation-corrected targeted molecular dynamics simulations (dcTMD) to understand such rare ligand unbinding pathways in proteins. By applying a moving distance constraint along a pre-selected reaction coordinate, we obtained better sampling. Our study on the G protein-coupled receptor A2A revealed different ligand unbinding pathways connected to ligand-lipid interactions. Furthermore, we combined stereographic force spectroscopy with biased MD simulations to gain insights into the influence of directional forces in the streptavidin-biotin complex.

 

 

Modeling quantum transport through nanosystems containing coupled electronic and vibrational degrees of freedom is a challenging problem that requires sophisticated transport methods. The underlying physics of such transport scenarios is, however, highly interesting, with connections to a wide range of fields and systems, such as molecular junctions or scattering of molecules off metal surfaces. In general, therefore, developing methods that can describe transport through such nanosystems in a physically interpretable manner is a crucial task.

In this talk, a newly-developed semi-classical approach for modeling such transport scenarios is introduced. In this treatment, the vibrational degrees of freedom are treated classically as influenced by quantum electronic degrees of freedom, which manifest through current-induced forces like electronic friction. In contrast to previous formulations of electronic friction, this approach is based on the numerically exact hierarchical equations of motion approach, which can treat not only strong molecule-lead couplings but also strong interactions in the nanosystem.

To demonstrate the new approach, the current-induced forces for several nanosystems are discussed. First, a single level coupled to a single vibrational degree is explored, with particular emphasis on how the diffusion and electronic friction relate to vibrationally-assisted electron-hole pair creation in the electrodes. We then explore how the addition of a second, high-frequency mode, which must be treated quantum mechanically, affects the current-induced forces of the classical mode, finding negative friction in a particular parameter regime. Finally, we explore the parameter regimes in which the semi-classical approach can correctly reproduce the transport dynamics of the numerically exact fully quantum treatment.