[Raj Choudhary]

Dear Sir

Is there any accepted quantitative correlation between experimentally observed percentage of inhibition and MMPBSA binding energy? 

For example, if a drug candidate A is showing an experimental inhibition of 80% while candidate B is showing an inhibition of 30% at the same concentration, what difference in their MMPBSA binding energy may be expected?

Thank you in advance

Best regards

Raj Choudhary

[marioe911116]

Well it's a little bit complicated to answer the question without previous knowledge of the system, but a way to go here could be trying to generate IC50 values and those are the ones typically used to perform comparison with MMPB(GB)SA

[Raj Choudhary]

Thank you sir for the clarification. I will interpret the results accordingly.

Best regards

--
You received this message because you are subscribed to the Google Groups "gmx_MMPBSA" group.
To unsubscribe from this group and stop receiving emails from it, send an email to gmx_mmpbsa+...@googlegroups.com.
To view this discussion on the web visit https://groups.google.com/d/msgid/gmx_mmpbsa/d0ccd537-c008-44a7-8766-1ca938a07377n%40googlegroups.com.
For more options, visit https://groups.google.com/d/optout.

[Raj Choudhary]

Dear Sir

For the inhibitory action against the particular enzyme, the IC50 for compound A was found to be around 11micromolar, while that for B was around 23 micromolar concentration of the respective drug molecules.

 Is it now possible to have a rough idea regarding what might be the expected difference in their MMPBSA binding energies? 

Thank you

Best regards

Raj Choudhary

[Mario Sergio Valdes]

Normally, a lineal regression parameterization is used to correlate the experimental energy with the theoretically estimated energy of several similar systems (set of reported inhibitors of a receptor in question). Therefore, it is not easy to estimate the expected differences in this case, but it can be expected to correctly classify both ligands (although it depends on the estimation error).

[marioe911116]

∆∆G[A-B]≈RT*ln(IC50[A]) - RT*ln(IC50[B])

assuming T=310K, then:

∆∆G≈0.002*310*Ln(11E-06) - 0.002*310*Ln(23E-06)

∆∆G≈-0.46kcal/mol (expected difference)

[Raj Choudhary]

Dear Sir

Thank you so much for your kind help. I really appreciate. Your explanation is very useful.

Best regards

Raj Choudhary

To view this discussion on the web visit https://groups.google.com/d/msgid/gmx_mmpbsa/3e070dd1-0fc0-4bad-9968-75536bdfeb14n%40googlegroups.com.

[Raj Choudhary]

Dear Sir

Can you kindly help me to understand the physical significance of del EPB and del ENPOLAR that are obtained as the energy components in a MM-PBSA output file? Under what situations will a ligand (within the protein-ligand complex) show a higher positive EPB? Is there a way to reduce it?

[marioe911116]

EPB and ENPOLAR are the polar and non-polar components of the solvation energy calculated with the PB model. Further information about these terms can be found in our introduction section 

https://valdes-tresanco-ms.github.io/gmx_MMPBSA/dev/introduction/

[Raj Choudhary]

Ok, thank you sir for the reference. 

Best regards

Raj Choudhary

--

You received this message because you are subscribed to the Google Groups "gmx_MMPBSA" group.
To unsubscribe from this group and stop receiving emails from it, send an email to gmx_mmpbsa+...@googlegroups.com.

To view this discussion on the web visit https://groups.google.com/d/msgid/gmx_mmpbsa/ea2aa1d4-7bf8-4f53-a46b-4db1c7aaa971n%40googlegroups.com.