<h3>Title</h3>
<p><span style="color: #0000ff;">Coarse-grained simulations of biomolecules: from peptides to large assemblies</span></p>
<p><strong><span style="text-decoration: underline;">Abstract</span> :</strong></p>
<p>In my first talk, I illustrated how coarse-graining the energy landscape to its bare essentials (stationary points) can be an effective means of studying biomolecular folding and dynamics over time-scales that are not accessible by standard simulation techniques. Here, I will illustrate how coarse-graining the degrees of freedom (resulting in a simplified representation of the energy landscape) can also be a viable route towards understanding key biophysical phenomena. In this context, I will illustrate how coarse-grained simulations of peptide monomers could provide a microscopic basis for the apparent anomaly observed in the aggregation rates of Ab40 and Ab42. I will show that despite having identical ensemble-averaged properties, reminiscent of random coils, the monomer conformational ensembles of the two sequences encode cryptic signatures of the aggregation-prone (N*) fibrillike states. The nearly one order of magnitude difference between the aggregation rates of Ab40 and Ab42 can be quantitatively explained in terms of the relative populations of the N* states. Interestingly, the transitions to fibril-like states appear<br />to follow Ostwald’s rule of stages. </p>
<p>Finally, I will present a roadmap to my future research, which will exploit both flavors of coarse-graining to provide molecular insights into functional, as well as aberrant assembly phenomena in biology. Specifically, I will discuss how I plan to answer some intriguing questions related to the hierarchical organization of the genome, as well as liquid-liquid phase separation, and its potential link to protein aggregation diseases.</p>