Hi,
I'd follow mostly the same protocol as a relative binding free energy (where ligand a transforms to ligand b), but instead of having a ligand b, your timask, scmask of those regions becomes nothing
timask2='', scmask2='',
I would also apply the virtual bond algorithm described here to keep your ligand in the pocket (described as a virtual bond here)
https://pubs.acs.org/doi/pdf/10.1021/jp505777n
These calculations are fairly expensive to calculate. Relative binding free energies converge a lot more quickly because the amount of phase space to sample is already somewhat more limited due to the presence of a ligand you already know its binding pose/pocket position. The less data you know about your system, the less likely you'll place your ligand correctly, and simple changes such as having a side chain incorrect, could vastly give different absolute binding free energy values.
-Charlie
On 10/1/19, 4:26 PM, "Debarati DasGupta" <debarati_dasgupta.hotmail.com> wrote:
CAUTION: EXTERNAL EMAIL
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.
Thanks
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Received on Wed Oct 02 2019 - 08:30:02 PDT
