CCB Brown Bag Seminar: Recovering the Rates from Metadynamics Simulations (Pilar Cossio)

Speaker: Pilar Cossio, Ph.D.,  Tandem Group Leader, Max Planck Institute of Biophysics & and University of Antioquia

Topic: Recovering the rates from metadynamics simulations

Metadynamics enables the efficient exploration of the conformational space
of a system. However, the dynamic information of the system is lost due to
the bias acceleration. Recovering the transition rates from these
simulations is possible using infrequent metadynamics, where the average
time of escape is, typically, estimated from a fit to a Poisson
distribution using rescaled times. Here, we propose an alternative method
for extracting the rate coefficients based on a maximum likelihood
formalism when the unbinding times following Poisson statistics. However,
when the dynamics is not Poissonian (e.g., because of the use of a poor
collective variable), we propose a correction to the average rescaled time
based on Kramers' theory using Jarzynski's equality to estimate the
barrier. An additional approximation allows us to correct the individual
rescaled times for recovering a Poissonian behavior. We tested the methods
over a variety of systems, finding that the transition rates have equal or
better accuracy than those extracted with other methods. In the cases
where Poissonian statistics fail, we find that the corrections greatly
improve the estimated rate.

Since 2016, Pilar Cossio is a Max Planck Tandem Group Leader associated with the University of Antioquia (Colombia) and the Max Planck Institute of Biophysics (Germany). She earned a B.S. in physics from the University of Antioquia in 2007 and a Ph.D. in physics and chemistry of biological systems from the International School for Advanced Studies (SISSA) in Italy in 2011. She held postdoctoral positions at the National Institutes of Health (NIH, USA) and at the Max Planck Institute of Biophysics. Her main focus is the development of mathematical and computational methods to characterize proteins’ structures and dynamics from cryo-electron microscopy, single-molecule spectroscopy and biomolecular simulations.