2 research outputs found
Statistical Inference of Rate Constants in Chemical and Biochemical Reaction Networks Using an “Inverse” Event-Driven Kinetic Monte Carlo Method
The
use of rate models for networks of stochastic reactions is
frequently used to comprehend the macroscopically observed dynamic
properties of finite size reactive systems as well as their relationship
to the underlying molecular events. Τhis particular approach
usually stumbles on parameter derivation associated with stochastic
kinetics, a quite demanding procedure. The present study incorporates
a novel algorithm, which infers kinetic parameters from the system’s
time evolution, manifested as changes in molecular species populations.
The proposed methodology reconstructs distributions required to infer
kinetic parameters of a stochastic process pertaining to either a
simulation or experimental data. The suggested approach accurately
replicates rate constants of the stochastic reaction networks, which
have evolved over time by event-driven Monte Carlo (MC) simulations
using the Gillespie algorithm. Furthermore, our approach has been
successfully used to estimate rate constants of association and dissociation
events between molecular species developing during molecular dynamics
(MD) simulations. We certainly believe that our method will be remarkably
helpful for considering the macroscopic characteristic molecular roots
related to stochastic physical and biological processes
Switching of Protonation Sites in Hydrated Nicotine via a Grotthuss Mechanism
The switching of the protonation
sites in hydrated nicotine, probed
by experimental infrared (IR) spectroscopy and theoretical ab initio calculations, is facilitated via a Grotthuss instead
of a bimolecular proton transfer (vehicle) mechanism at the experimental
temperature (T = 130 K) as unambiguously confirmed
by experiments with deuterated water. In contrast, the bimolecular
vehicle mechanism is preferred at higher temperatures (T = 300 K) as determined by theory. The Grotthuss mechanism for the
concerted proton transfer results in the production of nicotine’s
bioactive and addictive pyrrolidine-protonated (Pyrro-H+) protomer with just 5 water molecules. Theoretical analysis suggests
that the concerted proton transfer occurs via hydrogen-bonded bridges
consisting of a 3 water molecule “core” that connects
the pyridine protonated (Pyri-H+) with the pyrrolidine-protonated
(Pyrro-H+) protomers. Additional water molecules attached
as acceptors to the hydrogen-bonded “core” bridge result
in lowering the reaction barrier of the concerted proton transfer
down to less than 6 kcal/mol, which is consistent with the experimental
observations