Heating and Cooling Strategy to Improve Estimates of CYFIP1p-Derived Peptides’ Helicity Probabilities in Biased Molecular Dynamics Simulations

Post date: Feb 24, 2019 10:31:53 PM by Irene Rostovsky

A CYFIP1p-derived peptide in VMD: bond lengths of 2.5 Å (units used by VMD) or less

for the middle three bonds would indicate a helical structure.

By Irene Rostovsky

Since the binding region of CYFIP1p can be used as a model for a precursor molecule for the development of a drug to treat Fragile X syndrome and cancer, we wanted to calculate the probability of finding the peptide corresponding to this binding region, and another peptide differing by one residue, in a helical conformation. Due to the difficulty of attaining convergence of random and helical starting conformations for one of our peptides, we performed a series of simulations at 6.25 kJ/mol bias force (previously determined as the optimal force by Megan Wang), where we manipulated temperatures in a manner that is similar conceptually to replica exchange, but is simpler to perform. We alternated between 400 K and 300 K for succeeding simulations to disturb the initial states and speed up exploration of different conformations. Our results so far suggest that alternating heating and cooling is an effective way to help peptides break out of their initial conformations, and form/ fully break alpha helices at a reasonable rate over 1 ms. The next step is to perform statistical analysis on our results and to test the possible convergence we have seen through our new heating/ cooling method.