Free Energy Surface and Molecular Mechanism of Slow Structural Transitions in Lipid Bilayers.

Lipid membrane remodeling, crucial for many cellular processes, is governed by the coupling of membrane structure and shape fluctuations. Given the importance of the ∼ nm length scale, details of the transition intermediates for conformational change are not fully captured by a continuum-mechanical description. Slow dynamics and the lack of knowledge of reaction coordinates (RCs) for biasing methods pose a challenge for all-atom (AA) simulations.

Computation of the Protein Conformational Transition Pathway on Ligand Binding by Linear Response-Driven Molecular Dynamics.

While extremely important for relating the protein structure to its biological function, determination of the protein conformational transition pathway upon ligand binding is made difficult due to the transient nature of intermediates, a large and rugged conformational space, and coupling between protein dynamics and ligand-protein interactions. Existing methods that rely on prior knowledge of the bound (holo) state structure are restrictive. A second concern relates to the correspondence of intermediates obtained to the metastable states on the apo → holo transition pathway.