1st Speaker: Alex Rautu, Ph.D., Flatiron Research Fellow, Biophysical Modeling
Topic: Active Hydrodynamic Theory of Chromatin Dynamics
The organization of the chromatin inside the cell nucleus is crucial for the function of eukaryotes, acting as a substrate for many nuclear processes. In differentiated cells, chromatin is also spatially segregated into euchromatin and heterochromatin compartments. The former is loosely packed and transcriptionally active, whilst the latter is densely compacted and mostly consisting of silent genes. Here we describe a hydrodynamic model of chromatin and nucleoplasm at the micron-size scales. The eu- and hetero-chromatin is modeled as a viscous, compressible fluid, as informed by microrheology experiments and their response at long time. The crosslinking interaction strength of heterochromatic components induces density and hydrodynamic instabilities, which drive large-scale fluid flows. Simulations reveal coarsening of heterochromatic components, which lead to a finite-size droplet in an open system, whereas in the case of a confining domain we observe a redistribution at the boundaries, resembling a wetting phenomenon. We believe that these mechanical processes may play an important role in the spatial organization of heterochromatin which is usually enriched near the nuclear periphery.
2nd Speaker: Doug Renfrew, Ph.D, Research Scientist, Systems Biology
Topic: Evaluating the Conformations and Dynamics of Peptoid Macrocycles
Peptoid macrocycles are versatile and chemically diverse peptidomimetic oligomers. However, the conformations and dynamics of these macrocycles have not been evaluated comprehensively and require extensive further investigation. Recent studies indicate that two degrees of freedom, and four distinct conformations, adequately describe the behavior of each monomer backbone unit in most peptoid oligomers. On the basis of this insight, we conducted molecular dynamics simulations of model macrocycles using an exhaustive set of idealized possible starting conformations. Simulations of various sizes of peptoid macrocycles yielded a limited set of populated conformations. In addition to reproducing all relevant experimentally determined conformations, the simulations accurately predicted a cyclo-octamer conformation for which we now present the first experimental observation. Sets of three adjacent dihedral angles (ϕi, ψi, ωi+1) exhibited correlated crankshaft motions over the course of simulation for peptoid macrocycles of six residues and larger. These correlated motions may occur in the form of an inversion of one amide bond and the concerted rotation of the preceding ϕ and ψ angles to their mirror-image conformation, a variation on “crankshaft flip” motions studied in polymers and peptides. The energy landscape of these peptoid macrocycles can be described as a network of conformations interconnected by transformations of individual crankshaft flips. For macrocycles of up to eight residues, our mapping of the landscape is essentially complete.
