Hi Dr. Luo,
Thank you for the suggestions! I tried a few things, and can I ask some follow up questions?
I performed autoimage and extracted the coordinates of N and P atoms of the lipid head groups with pytraj. Then, the thickness and Z-coordinate of the center of the membrane were calculated according to |N+P+ − N−P−| method from the paper.
1. Should I just set the calculated Z-coordinate of the membrane center to mctrdz keyword, or the relative distance between the membrane and protein centers? If I need to calculate the location of protein center, is it just the mean of Z-coordinates of the protein atoms, or the center of mass?
2. Since the thickness and center were calculated with the autoimaged trajectory, the same trajectory should be used to do the free energy calculation, right?
3. Is 2 reasonable for the fillratio keyword for a protein-ligand system?
4. Do you know the default value of mprob in Amber 16, I couldn’t find this parameter in the manual.
5. In nmode entropy calculation, what is a reasonable value for the distance-dependent dielectric constant (dielc) for a membrane protein system?
6. To optimize the parameter settings of MMPBSA calculation for my system, I need to calibrate the parameters by comparing the computational results with the actual experimental results, right?
Thank you so much!
Best wishes,
Haoxi
On Jun 11, 2020, at 10:27 AM, Ray Luo <rluo.uci.edu<mailto:rluo.uci.edu>> wrote:
[External Email]
Hi Haoxi,
The detail of the implicit membrane setup can be found in the following paper:
Journal of Chemical Theory and Computation 13 (7), 3398–3412, 2017
which addresses most of your questions. Briefly:
1. How can I find out the best position to put the membrane center (mctrdz) and the thickness (mthick)?
This is discussed in detail in the paper. You'll need to measure the
membrane thickness and its center for each snapshot by manipulating
the membrane coordinates from your MD trajectory. Remember to first
image all atoms into the unit cell using cpptraj. Then compute the
average thickness and center for the trajectory and use it in mmpbsa.
We will release a python script to facilitate the membrane setup in
the next release.
2. If the protein is just a receptor rather than ion channels, should I still set poretype=1?
It's not necessary.
3. In the sample input file for MMPBSA with membrane proteins in Amber manual, bcopt was set to 10 and eneopt to 1. But under the detailed explanation of eneopt option, it was emphasized that eneopt=1 requires a nonzero CUTNB and BCOPT = 5. What value should I use for bcopt and eneopt respectively?
You'll have to use BCOPT=10, the periodic boundary for membrane
proteins. BCOPT=5 is for water soluble proteins. ENEOPT=1 works for
both boundary conditions.
4. To run this calculation, I prepared 3 parameter/topology files (only complex, protein, ligand) and only kept protein and ligand in the MD trajectory. Is there any other files I need to make? In the MMPBSA tutorial on the website, the solvated parameter/topology file of the complex was also used via -sp option, but when I use it there was an error. Is it necessary to use the -sp option?
There is no difference between membrane proteins and globular proteins
in this regard. Please study the mmpbsa tutorials first to understand
the basic procedure.
5. Here are the parameter settings that I’m planning to use. Can I ask for some suggestions?
As for the keywords, please first use those in the mmpbsa test case
for the membrane proteins. Let's see what problem you still have after
addressing the above concerns.
All the best,
Ray
--
Ray Luo, Ph.D.
Professor of Structural Biology/Biochemistry/Biophysics,
Chemical and Materials Physics, Chemical and Biomolecular Engineering,
Biomedical Engineering, and Materials Science and Engineering
Department of Molecular Biology and Biochemistry
University of California, Irvine, CA 92697-3900
_______________________________________________
AMBER mailing list
AMBER.ambermd.org<mailto:
AMBER.ambermd.org>
https://urldefense.proofpoint.com/v2/url?u=http-3A__lists.ambermd.org_mailman_listinfo_amber&d=DwIGaQ&c=sJ6xIWYx-zLMB3EPkvcnVg&r=SSRyv2p8U1S1O1OKefEt8WnSpJO5RS47PLTtN6Y14jU&m=iypT555cNdqfN3g6QVYCvIEXtPEPEDKvSxOsjIVvSgA&s=C36L6Gyx1I1K_hKLojwZi3SqBtkoSmI2vdROR1b2SSo&e=
_______________________________________________
AMBER mailing list
AMBER.ambermd.org
http://lists.ambermd.org/mailman/listinfo/amber
Received on Wed Jun 17 2020 - 15:00:03 PDT
