Date: Fri, 24 May 2024 09:56:33 +0000
Dear Amber developers,
I'm trying to use the Constant pH Molecular Dynamics simulation to find the pKa value for a drug molecule as a "Free ligand" and as a "Ligand in a complex (Guest:Host); where the host is a macrocyclic compound".
First, I get the charge of the drug molecule by optimizing the structure then using the RESP method to get the charges.
second, I get the Reference Energy by following the tutorial "https://github.com/swails/cph-ref-demo" from Dr. Jason M Swails, then edit the titratable_residues.py file and recompile the AMBER.
After that a .cpin file were created using the cpinutil.py program, Finally a pH Replica Exchange MD simulation was preformed using an 8 replicas for 100ns.
For the free guest I got the same pKa value as the experimental one, but for pKa of the ligand in the complex I got a value far away for the experimental, In fact the pKa shift were surprisly correct but in the opposite direction.
The pKa values were experimentally; 1.0, 3.4 for the ligand in the free and complex form respectively (ΔpKa= 2.4)
The pKa values were by CpHMD; 1.0, -1.4 for the ligand in the free and complex form respectively (ΔpKa= - 2.4)
I have tried different solvation model (implicit, igb=2, and 5), and explicit (without ions); Also, I have tried the same thing for different drug and I got the same issue (opposite pKa shift).
Any thoughts to solve this matter
the input file for the pH Replica Exchange MD
*****
REM for CpH
&cntrl
icnstph=1, dt=0.002, ioutfm=1, ntxo=2,
nstlim=5000, ig=-1, ntb=0, numexchg=10000,
ntwr=10000, ntwx=1000, irest=1,
cut=1000.0, ntcnstph=5, ntpr=1000,
ntx=5, solvph=0.3, saltcon=0.1, ntt=3,
ntc=2, ntf=2, gamma_ln=10.0, igb=5,
/
****
Many Thanks in advance.
Best Regards,
Osama M. AbuHasan
PhD Student
.
Constructor University Bremen gGmbH
Campus Ring 1
28759 Bremen
Germany
[cid:678d3efd-6cff-4f15-8f2c-3494acb0bc48]
Commercial registry: Amtsgericht Bremen, HRB 18117
Chairs of the Executive Board (Vorsitzende der Geschäftsführung): Dr. Stanislav Protasov (President/Präsident), Oznur Bell (Chancellor/Kanzlerin)
Managing Directors (Geschäftsführung): Prof. Dr. Thomas Auf der Heyde, Maja Laetitia Feldt
Chairman of the Board of Governors (Aufsichtsratsvorsitzender): Dr. Serg Bell
_______________________________________________
AMBER mailing list
AMBER.ambermd.org
http://lists.ambermd.org/mailman/listinfo/amber
(image/png attachment: Outlook-3xxmqspf.png)
