It is becoming more and more difficult to publish the results of single simulations since questions on reproducibility and convergence arise so most practitioners tend to run multiple independent MD simulations with different initial conditions (ion distribution, structure, velocities, ...) with a minima of three replicates.
See this paper by Knapp: https://pubs.acs.org/doi/10.1021/acs.jctc.8b00391
--tec3
________________________________________
From: Cenk Andac <cenkandac.gmail.com>
Sent: Sunday, October 10, 2021 2:20 PM
To: amber.ambermd.org
Subject: [AMBER] How many complex trajectories for mmpbsa computations ?
Dear Amber community,
We have submitted a research manuscript to a scientific journal. The
manuscript is about MD simulations and MMPBSA binding energy
vomputations that involve extensive use of amber suite of programs.
We have 11 compounds ( 4 reference compounds + 7 compounds synthesized in
our laboratory) targeted to a protein. We have implemented ~370 ns MD
computations for each ligand+receptor system. Then we computed MM-PBSA
binding energies for each complex systems using 100 snapshots extracted
from the the last 24 ns of trajectory.
We then rank-ordered the binding energies.
In the manuscript we discussed binding energies for the reference and
synthesized compounds. We also put in the manuscript a nice picture of
averaged coordinates of the highest-affinity ligand in complex with its
receptor
One of the reviewers responded to us with the following request :
*Reviewers request:* A single MD simulation is not sufficient. For each
compound, three replicas of 200+ ns MD simulations should be performed.:
*Our respond: *Thank you for the invaluable comment.
running several MD simulations for a complex system will not affect MM-PBSA
computations much provided that the MD simulations equilibrated well. The
idea with MM-PBSA method is that multiple snapshots (best is more than 50!)
are collected over a certain time interval from equilibrated trajectory.
Energy computations are implemented for each snapshot and finally averaged
out to give rise to an average binding affinity value over dynamics motions
of the complex system at equilibrium in solution. Of course, different MD
simulations of the same complex system will yield different snapshots but
should give rise to very similar averaged MM-PBSA energies at equilibrium.
*The reviewer then responded* : Three replicas of 200+ MD simulations are
required for each compound to make sure that the simulation runs are
consistent, or to determine a way of using certain average. This was a
trend before and is a convention now in MD simulations.
My question here is that is it really necessary to run 3 replicas of MD
simulations to average out ligand+receptor interactions ?
Thanks in advance.
Jenk Andac.
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Received on Sun Oct 10 2021 - 16:00:03 PDT
