Nonequilibrium molecular dynamics via a nondiverging subtraction technique

Abstract

The subtraction technique is a powerful tool for studying nonequilibrium phenomena in manybody systems at short times. Its major limitation lies in the long-time noise due to the Lyapunov divergence of initially close trajectories in phase space. We present a method to compute transport coefficients even when long-time tails are present, with a subtraction technique modified by adding a kind of frictional force field to monitor the phase-space divergence. The price to be paid is to perform an extrapolation of the results to zero field.

Identification of the Initial Steps in Signal Transduction in the α4β2 Nicotinic Receptor: Insights from Equilibrium and Nonequilibrium Simulations

“…In each short simulation, the nicotine molecules were annihilated in the binding pockets, and the trajectory of these artificial APO systems (containing the receptor, membrane, solvent, and ions) was followed for 5 ns. The subtraction technique (Ciccotti et al, 1979;Paolini et al, 1990) was used to compare the short APO and NCT simulations (Figure S6) and identify the residues involved in signal transmission by canceling the noise coming from the intrinsic fluctuations of the systems. This approach allows for the identification of the receptor response to instantaneous removal of nicotine from both binding pockets (Figures 6, S6, and S7) and provides a detailed understanding of the associated conformational changes by averaging the difference in the position of the residues between the short APO and NCT simulations at specific time points (Video S2).…”

“…This annihilation of nicotine is not intended to represent the physical process of unbinding: it is to test the effect of this immediate perturbation on the system, via the subtraction technique, introduced by Ciccotti et al (Ciccotti et al, 1979;Paolini et al, 1990). This subtraction technique was used to analyse the simulations (as described previously (Damas et al, 2011;Oliveira et al, 2005)) and determine the response of the system to the annihilation of nicotine.…”

“…This subtraction technique was used to analyse the simulations (as described previously (Damas et al, 2011;Oliveira et al, 2005)) and determine the response of the system to the annihilation of nicotine. According to the subtraction technique (Ciccotti et al, 1979;Paolini et al, 1990), the fast response of a system to a perturbation can be directly measured by averaging the difference of a given property (in this case, the position of the C a atoms) in perturbed (APO) and unperturbed simulations (NCT) at a given time as long as the two simulations are highly correlated and providing that enough data is gathered. In highly correlated systems, the random fluctuations of the systems largely cancel, thus giving the time evolution of the response to the perturbation.…”