hteran
commented
1 year ago Hi,
We have run a number of FEP simulations on GPCRs, see as an example https://doi.org/10.1021/acs.jmedchem.0c01431 . But a few points are here needed for clarification: 1- In our case, we use the Berger parameters for the lipids in combination with the OPLS-AA for the protein, such parameters are indeed included in the OPLS2015.lib/prm files 2- The GPCR (usually in complex with a lead compound) was previously equilibrated with GROMACS/PBC indeed with anisotropic coupling of pressure, using our Pymemdyn package, (http://www.gpcr-modsim.org/) but importantly as a PRELIMINARY step before setting up the corresponding sphere for QligFEP simulations. 3- Our MD/FEP simulations use spherical boundary conditions thus anisotropic coupling of pressure does not apply. Basically the system from stage 2 is extracted, as a PDB of teh final stage of te Pymemdybn equilibration stage, this is all explained in the corresponding A2A example on the QligFEP paper https://jcheminf.biomedcentral.com/articles/10.1186/s13321-019-0348-5#Sec2
This says, if you want to use a GPCR system previously equilibrated on the membrane with CHARMM and you want to use that forcefield, it is available in the QligFEP distribution, BUT you have to implement there the corresponding POPC parameters, this is not yet included in the distribution. This involves some translation of the CHARMM to Q syntax to build the corresponding entry on the CHARMM36.lib file and also the new parameters added on the corresponding sections of the CHARMM36.prm file. Would you do so, please communicate to us and upload to a separate branch, as indicated on the GPLv2 license? We are happy to provide further technical assistance if needed.
May I ask you about your name/affiliation, easier to know who we are talking to ;-)
My best,
Hugo
Hugo Gutierrez de Teran, PhD. Senior Lecturer in Computational Biochemistry Department of Cell and Molecular Biology Uppsala University BMC, Box 596 SE-751 24 Uppsala (SWEDEN)
Phone: +46(0)18 471 5056 e-mail: @.**@.> GPCR-ModSim: www.gpcr-modsim.orghttp://www.gpcr-modsim.org/
On 12 Oct 2023, 06:40 +0200, xy127 @.***>, wrote:
Hello, Could you add a tutorial of simulating GPCR proteins ? In the second step of preparing proteins, protprep.py can't recognize lipids (in my case POPC lipids prepared in Charmmgui) and therefore no protein.pdb is produced. Also, since membrane MD/FEP simulation involves anisotropic coupling of pressure ,in XY and Z direnction, is the third step(set up FEP) also different from CDK2 example? Thank you.
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Hello, Could you add a tutorial of simulating GPCR proteins ? In the second step of preparing proteins, protprep.py can't recognize lipids (in my case POPC lipids prepared in Charmmgui) and therefore no protein.pdb is produced. Also, since membrane MD/FEP simulation involves anisotropic coupling of pressure ,in XY and Z direnction, is the third step(set up FEP) also different from CDK2 example? Thank you.