AMBER Archive (2005)

Subject: Re: AMBER: MM_PBSA_parameter

From: Wei Chen (gtg553p_at_mail.gatech.edu)
Date: Wed Nov 23 2005 - 16:51:16 CST

Hi, Ray,

I used RADIOPT=1 and PRBRAD=1.6. It gave me a worse result.
If I set RADIOPT=0, the cavity radii will be read from prmtop files. Does this
mean that I use PARSE radii?

I haven't used the bugfix. But my system has +3 charges, not neural.

PBSA output and input are deleted automatically after mm_pbsa done. I will
check them.

Thank you very much!

Wei Chen

Quoting Ray Luo <rluo_at_uci.edu>:

>
> >Then I ran MM_PBSA for my system. Due to the
> >large size of my system, I have to decrease the "SCALE" to 1.5. The topology
> >file I use is generate by tleap with default parameters. Total 150 snapshots
> >extracted from 3ns trajectory. The GB gives a negative value with small SD.
> But
> >PB gives a large positive value with large SD. I do not know what is wrong.
> >Then I tried to change some parameters. I set "PRBRAD" to 1.5 or 1.4. I got
> >very different answers. So my question is how to choose "PRBRAD". What does
> it
> >exactly mean to "use 1.4 with the PARSE parameter set and 1.6 with the radii
> >optimized by R. Luo"? What is PARSE parameter set and what is R. Luo
> parameter
> >set?
> >
> >
>
> On the larger SD for PB, have you patched the last pbsa bugfix? If you
> have, this is most likely due to the larger grid spacing that you used,
> i.e. a smaller SCALE value. Also, could you show us your pbsa input and
> output files? There is no enough information for us to tell what is
> happening.
>
> If you use RADIOPT of 1 for pbsa, then PRBRAD of 1.6 should be used
> because this is the value in the PB cavity radii optimization performed
> by our group. If you use the parse cavity radii set, you need to use
> 1.4, again because this is the valued used in the parse cavity radii
> optimization performed by Kim Sharp.
>
> It's not very surprising that PB/GB results are highly dependent on what
> radii are used. There is nothing wrong about it just as molecular
> dynamics simulations strongly depend on van der Waals parameters,
> charges and other parameters. Unfortunately, there are no overwhelming
> evidences as for which set of radii are better with the Amber charges
> because there are not enough data to constrain the value of PB/GB cavity
> radii. This is still an ongoing research in many groups.
>
> Further, PB results also depend on PRBRAD, i.e. water probe radius,
> which is used to determine where water molecules can go or not in a
> complex molecular environment. GB's dependent on PRBRAD is not visible
> to end users because it's used in its parameter optimization process.
> However, due to cancellation of errors, relative binding free energies
> in general depend less on these parameters than absolute binding free
> energies, and much less than conformational free energies.
>
> >Another question is how I can make sure the solution of PB already converges
> if
> >I only set "LINIT" to certain number. Why is the "SURFTEN" different for PB
> and
> >GB? Why do we calculte the absolute reaction field energy ("REFE"=0) instead
> of
> >the difference of reaction field energy ("REFE">0) to calculate the binding
> >free energy?
> >
> >
> >
> You can find out whether PB has converged by looking at the pbsa output
> file. This might be another reason that you saw larger SD for PB
> results. There should be a warning on convergence failure in the output
> file if PB doesn't converge. Also, if you set "npbverb=1" in your pbsa
> input, you can find out more info on your pbsa run.
>
> Finally, the SURFTEN value for PB is used when the PB cavity radii set
> (RADIOPT=1) was optimized by our group. I think the SURFTEN for GB is
> taken from the parse radii set. However, the difference in SURFTEN won't
> change your result noticeably because the difference is very small.
>
> All the best,
> Ray
>
> --
> ====================================================
> Ray Luo, Ph.D.
> Department of Molecular Biology and Biochemistry
> University of California, Irvine, CA 92697-3900
> Office: (949)824-9528 Lab: (949)824-9562
> Fax: (949)824-8551 e-mail: rluo_at_uci.edu
> Home page: http://rayl0.bio.uci.edu/rayl/
> ====================================================
>
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