Accelerated molecular dynamics (aMD) is an enhanced sampling technique that works by flattening the molecular potential energy surface, often by adding a non-negative boost potential when the system potential is lower than a reference energy. The boost potential, ΔV decreases the energy barriers and thus accelerates transitions between different low-energy states. With this, aMD is able to sample distinct biomolecular conformations and rare barrier-crossing events that are not accessible to conventional molecular dynamics (cMD) simulations. AMD has been successfully applied to a number of biological systems and hundreds-of-nanosecond aMD simulations have been shown to capture millisecond-timescale events in both globular and membrane proteins. In addition, it is appealing to reweight aMD trajectories to recover canonical ensemble and the original free energy profile of functional biomolecules. Here, we provide a toolkit of python scripts "PyReweighting" to facilitate the reweighting of aMD simulations. PyReweighting implements a list of commonly used reweighting methods, including (1) exponential average that reweights trajectory frames by the Boltzmann factor of the boost potential and then calculates the ensemble average for each bin, (2) Maclaurin series expansion that approximates the exponential Boltzmann factor, and (3) cumulant expansion that expresses the reweighting factor as summation of boost potential cumulants.
PyReweighting-1D.py
reweight-1d.sh ./reweight-1d.sh $Emax $cutoff $binx $data $T
PyReweighting-1D.py
test-PyReweighting.tgz
#################################################### #################################################### # Reweighting using cumulant expansion # Reweighting using Maclaurin series expansion # Reweighting using exponential average # NOTE: Check out cumulant expansion to the 2nd order "pmf-Psi-reweight-CE2.xvg"; normally it gives the most accurate result! #################################################### # Reweighting using cumulant expansion # Reweighting using Maclaurin series expansion # Reweighting using exponential average #################################################### #
Miao Y, Sinko W, Pierce L, Bucher D, Walker RC, McCammon JA (2014) Improved reweighting of accelerated molecular dynamics simulations for free energy calculation. J Chemical Theory and Computation, 10(7): 2677-2689. Miao Y, Bhattarai, A and Wang, J (2020) Ligand Gaussian accelerated molecular dynamics (LiGaMD): Characterization of ligand binding thermodynamics and kinetics, BioRxiv, https://doi.org/10.1101/2020.04.20.051979. ◇ Last updated: Dec 30, 2014 ◇ |