Gerhard Stock: "How Complex is the Dynamics of Protein Folding?"

Gerhard Stock
Biomolecular Dynamics, Institute of Physics, Albert Ludwigs University Freiburg Germany

How Complex is the Dynamics of Protein Folding?

Classical all-atoms molecular dynamics simulations are able to capture the structure, dynamics, and function of biomolecules in microscopic detail. Generating huge amounts of data, however, these simulations pose the problem of analyzing -and understanding- the computational results. To extract the essential information, we employ dimensionality reduction methods which reduce the complex and highly correlated biomolecular motion from 3N atomic coordinates to a few collective degrees of freedom. Along these reaction coordinates, we construct the free energy landscape of the system and characterize its metastable conformational states as well as the barriers connecting these states. Adopting various small peptides and proteins, we perform Langevin simulations on these low-dimensional energy landscape that facilitate a detailed investigation of the reversible folding of these systems. The approach allows us to address various questions, including:

* Is the energy landscape characterized by well-defining basins or tiers, i.e., is the dynamics hierarchic?

* Does the funnel model or rather a network of metastable states describe the folding process appropriately?

* What's the connection between fast conformational fluctuations and slow functional motions?

* What's the (minimal) dimensionality of the free energy landscape to correctly describe the dynamics, i.e., how much detail is required?