Dresden 2017 – wissenschaftliches Programm
BP 56.3: Vortrag
Donnerstag, 23. März 2017, 15:45–16:00, SCH A251
Time-resolved observation of allosteric communication in PDZ2 domain — •Gerhard Stock, Sebastian Buchenberg, and Florian Sittel — Institute of Physics, Albert Ludwigs University, Freiburg
A local perturbation of a protein may lead to functional changes at some distal site. A well-established example are PDZ domains which show an allosteric transition upon binding to a peptide ligand. Recently Hamm and coworkers (PNAS 2013) presented a time-resolved study of this transition. Using well-defined photopreparation and structure-sensitive infrared probing, they showed that the conformational rearrangement of PDZ2 occurs in a highly nonexponential manner on various timescales from pico- to microseconds.
Here we present extensive (in total 0.4 ms) nonequilibrium molecular dynamics simulations (all atom/explicit solvent) of Hamm's experiment, which allow us to monitor protein allosteric communication in real time. Along these lines, we address the following issues: What are the timescales of the transition and is there a hierarchy of processes? Is allosteric communication in PDZ2 dominated by enthalpic or entropic effects? Can the process be described as directed motion (domino picture), a simple barrier crossing, or rather via a diffusive heterogeneous transition path ensemble? Is allostery connected to the protein's pathways of energy transport? What's the role of the solvent? Does the long-range conformational rearrangement due to ligand binding occur via population-shift or induced-fit mechanism?