[AMBER] Thermodynamic integration

From: Debarati DasGupta <debarati_dasgupta.hotmail.com>
Date: Tue, 1 Oct 2019 20:25:59 +0000

Dear All,

I have been trying to read more about free energy calculations using TI method implemented in AMBER18. I recently did a webinar by CCG group wherein in MOE2019 they have incorporated the TI implementation setup collaborating with AMBER.

I did read this publication too from Professor Carlos Simmerling’s webpage “ https://chemrxiv.org/articles/Blinded_Prediction_of_Protein-Ligand_Binding_Affinity_Using_Amber_Thermodynamic_Integration_for_the_2018_D3R_Grand_Challenge_4/8312375/1”
This did throw a lot of light on how to exactly setup TI calculations in AMBER.

I still have a very fundamental question, it may be very stupid, but I am not sure how to setup TI to calculate the absolute binding affinity of a ligand towards a protein.
Is there something I am missing totally?
My protein of interest is ABL-kinase and I have a done some co-solvent simulations to get some hotspots( areas of possible ligandibility); I need to calculate the binding affinity of these small cosolvents towards ABL.
TI methods give us a “deldelG”, which is relative binding affinity, if we have a receptor (say CathepsinS) and have a set of 10+ ligands with a common core (scaffold).
If I have one protein +1 ligand and I need to calculate the binding affinity what is the procedure to be adopted?
Is there a tutorial to do that?

I am not looking to do MMGBSA/PBSA on this system.


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Received on Tue Oct 01 2019 - 13:30:01 PDT
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