Re: [AMBER] A confused question about calculate the binding free energy from MMPBSA.py

From: Ray Luo <rluo.uci.edu> Date: Fri, 29 Mar 2019 10:38:02 -0400

--
Ray Luo, Ph.D.
Professor of Structural Biology/Biochemistry/Biophysics,
Chemical Physics, Biomedical Engineering, and Chemical Engineering
Department of Molecular Biology and Biochemistry
University of California, Irvine, CA 92697-3900
On Thu, Mar 28, 2019 at 8:30 AM bjyx20090941 <bjyx20090941.163.com> wrote:
>
> Dear amber:
>     I have a confused question about calculate the binding free energy from MMPBSA.py.
>
>  Recently, I am learning how to calculate the binding free energy of receptor-ligand complex in solvated environment with MMPBSA module. And now I am repeating the example of ras-raf complex in amber tutorial. But I am confused by the result as follows due to the different versions of amber, such in tutorial the result is came from amber10,and my result is come from amber16.
>
>        I found that some parameters have changed as default values, example parameters of inp and radiopt. I have compared the results in listed:
>
> Table 1.The average binding free energy without entropy effect of 50 frames from different amber versions (kcal/mol）
>
> |
>
>
>
> |
>
> Amber10(yours)
>
> |
>
> Amber16(me)
>
> |
> |
>
> Different parameter
>
> |
>
> ipb=1,
>
> inp=1, radiopt=0
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> |
>
> ipb=2,
>
> inp=2, radiopt=1
>
> |
> |
>
> ΔEmm
>
> |
>
> -1025.4769
>
> |
>
> -1060.0425
>
> |
> |
>
> ΔEPB
>
> |
>
> 946.4251
>
> |
>
> 978.3053
>
> |
> |
>
> ΔENpolar/Cavity
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> |
>
> -7.3062
>
> |
>
> -51.5872
>
> |
> |
>
> ΔEdisper
>
> |
>
> --
>
> |
>
> 102.4891
>
> |
> |
>
> ΔGbinding (no ΔS)
>
> |
>
> -86.3579
>
> |
>
> -30.8353
>
> |
>
> In your results, the binding of ras_raf complex is favored although this is not real binding free energy.
>
> |
> | | | |
> | | |
>
>
>
>
> While I have done a test for choosing different parameters in amber16 with 5 frames as following:
>
> Table 2：The average binding free energy with entropy effect of 5 frames from amber16 by choose different parameters (kcal/mol）
>
> |
>
>
>
> |
>
> Inp=0
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>
> Inp=1
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>
> Inp=2
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> |
>
>
>
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>
> Radiopt=0
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>
> Radiopt=1
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>
> Radiopt=0
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>
> Radiopt=0
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>
> Radiopt=1
>
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> |
>
> ΔEmm
>
> |
>
> -1060.0425
>
> |
>
> -1060.0425
>
> |
>
> -1060.0425
>
> |
>
> -1060.0425
>
> |
>
> -1060.0425
>
> |
> |
>
> ΔEPB
>
> |
>
> 969.7617
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> |
>
> 978.3053
>
> |
>
> 969.7617
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> |
>
> 969.7617
>
> |
>
> 978.3053
>
> |
> |
>
> ΔENpolar
>
> |
>
> --
>
> |
>
> --
>
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>
> -7.5509
>
> |
>
> -51.5872
>
> |
>
> -51.5872
>
> |
> |
>
> ΔEdisper
>
> |
>
> --
>
> |
>
> --
>
> |
>
> --
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>
> 107.2185
>
> |
>
> 102.4891
>
> |
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>
> ΔSentropy
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>
> -42.0761
>
> |
>
> -42.0761
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> |
>
> -42.0761
>
> |
>
> -42.0761
>
> |
>
> -42.0761
>
> |
> |
>
> ΔGbinding (no ΔS)
>
> |
>
> -90.2807
>
> |
>
> -81.7371
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> |
>
> -97.8316
>
> |
>
> -34.6494
>
> |
>
> -30.8353
>
> |
> |
>
> ΔGbinding (ΔS)
>
> |
>
> -48.2047
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> |
>
> -39.662
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> |
>
> -55.7555
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> |
>
> 7.4267
>
> |
>
> 11.2409
>
> |
>
>    Actually, we can see that the binding eneries with entropy effect are differents  with regulating the parameters.
>
>    The default parameter result of amber16 is 11.2409 kcal/mol withinp =2 and radiopt=1,while the binding free energy is -55.7555 kcal/mol with inp =1 and radiopt=0. Which result i can trusted and used ?
>
>    So I am  very confused of this default parameter result with taking depersion energy into account. And what is the favor of parameter of inp =2 comparing to inp=1.
>
> I really hope to hear from you as soon as possible!
> Best Wishes
>
>
>
> Fangjia Fu
>
>
>
>
>
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