Re: what's the latest on using NAMD (and MD in general) for docking?

From: Thomas Evangelidis (
Date: Wed Mar 20 2019 - 18:42:16 CDT

On Wed, 20 Mar 2019 at 19:21, Homeo Morphism <>

> Is there any sense in putting receptor and putative ligand close to each
> other and run MD simulation to let ligand explore the receptor's accessible
> surface area to possibly find the docking site (or several)?
Short answer: don't try it unless you have access to Anton. Use instead
binding site prediction software (there are plenty of online tools for
that) and a robust docking software (I would go for Glide or Gold,
certainly not for AutoDock!) to generate several alternative protein-ligand
complexes. Think wisely on which receptor structure/conformation to dock
this ligand! Then run a short MD for each of them to equilibrate it with
explicit water. Also remember to optimize the ligand force field if needed.
At the end use some binding energy prediction method (like MM/GBSA) to rank
the possible complexes and select the most probably binding pose from the
top scored ones using your chemical intuition or any experimental evidence
that you have.

> I've looked through the mailing list and the overall mood is that of
> skepticism. But many messages date back to more than 5 years ago, that is
> before the super-fast GPUs that we have now. Was this skepticism due to
> computational constraints that people were under at the time or are there
> more substantial reasons why this shouldn't be attempted, with or without
> new-generation hardware?
> Here's the particular simulation I would like to try. We have a ligand. We
> know experimentally that it activates certain receptor. We have even
> narrowed down the area where it docks. And it's in a good agreement with
> Autodock results. Now the ligand is modified -- it's appended with another
> molecule at its one end. Autodock still docks the original part of the
> ligand to the receptor letting the modifier part dangle, but there's every
> reason to believe that in reality the modifier part will prevent the
> docking. If we only had one modifier part, we could check it
> experimentally, but we have more than a few.
> But what if I put every one of these modified ligands against the receptor
> and let them explore the receptor's surface in NAMD, watching for the most
> stable co-conformations, particularly in the area of interest, over
> hundreds of nanoseconds, possibly microseconds? How plausible is the whole
> approach?
> Thanks,
> Oleg

Dr Thomas Evangelidis
Research Scientist
IOCB - Institute of Organic Chemistry and Biochemistry of the Czech Academy
of Sciences <>
Prague, Czech Republic
CEITEC - Central European Institute of Technology <>
Brno, Czech Republic

This archive was generated by hypermail 2.1.6 : Tue Dec 31 2019 - 23:20:38 CST