Running gmx_mmpbsa with explicit water molecules

[Harold Grosjean]

Hello,

I virtually screened potential ligands and I would like to re-score them with gmx_MMPBSA. My target is a bromodomain and, therefore, interactions with water molecules is an important factor in ligand binding. I would like to run mmpbsa calculation with explicit water molecules around the ligand. These would be considered to be a part of the receptor. I am unable to find documentation about running such calculation. Is that possible or is there a hack around to make it possible?

Also, given that I is possible to run such calculation, should I keep water molecules in the apo only simulation?

Many thanks in advance for your help.

Regards,

Harold Grosjean

[Mario Sergio Valdes]

Hi Harold and welcome!

Unfortunately, at this time, not in this application. It is one of the calculations that we want to implement.

At the moment, the development of gmx_MMPBSA is on hold since the article is in the revision process.

You can consult the Nwat-MMGBSA articles that describe this methodology.

As soon as we publish the article, we will be implementing this and other methodologies.

Best wishes!

Mario S

[Harold Grosjean]

Hi Mario,

I hope you are well. Are you planning on incorporating calculations with explicit water molecules any time soon? I am currently running MMGBSA with IE and for charged ligand the computed -TdS is surprisingly high. I am under the impression that some charges are not buffered by water molecules which are then computed as repulsion between the protein and the ligand.

Many thanks in advance,

Harold Grosjean

[Mario Sergio Valdes]

Hi Harold.

Definitely. Currently, I am extremely busy with two reviews that I have to send in mid-December, but version 1.5.0 is almost ready. We will probably include these calculations for version 1.5.1 that we will try to release at the end of January.

Please review the internal dielectric constant values for loaded systems and the clarifications we have made regarding IE in the documentation. In version 1.5.0 we are covering the reported bugs, the necessary improvements for greater reliability and interpretability of IE, and many improvements in gmx_MMPBSA_ana.

We look forward to helping you.

Sincerely.

Mario S.