AMBER Archive (2005)

Subject: Re: Re: AMBER: MM-PBSA in protein-Zn-ligand system

From: Yong Xu (yxu_at_mail.sioc.ac.cn)
Date: Tue Apr 12 2005 - 22:17:00 CDT

Dear, Kara Di Giorgio,

I fit acoording to Calpha, the Ca2+ rmsd is about 1.5-2.0A, I didn't detect the change of residue near Ca2+, But I think it is not very bad.

one method to solve this problem, I think, is to restraint distance between Ca and it's neighbor residues.
How far your stuctral Ca go?

>I'm also trying to model a MMP. What did you do to keep you Ca2+ in
>your protein? I'm having the problem that my structural Ca keep flying
>out of my protein during a MD run.
>
>Thanks,
>
>Kara Di Giorgio
>
>
>On Apr 12, 2005, at 6:37 PM, Yong Xu wrote:
>
>> Dear Case and Holger
>>
>> I perform MM-PBSA calculation on MMP (metalloproteinase) which include
>> 2 Zn+ and 2 Ca2+. What confused me is that the result deltaG value is
>> not at the same order with experimental deltaG.
>>
>> the ki value is at the range of 10-1000nm, while my MM-PBSA result is
>> as following
>> MMPBSA:PBTOT -75 --- -85 kcal/mol
>> TdeltaS:TSTOT -18 --- -19 kcal/mol
>> so the deltaG_calc is at the range of -55 --- -65kcal/mol.
>> from above data (I finished three MD of MMP-ligand systems),
>> qualitative correlation can be obtained, but quantitative result is
>> very bad.
>>
>> WHAT I WANT TO KNOW is that
>> (1)should I set "protein + 2*ZN + 2*Ca" as receptor (above result is
>> from this setting).
>> (2)does this large detaG_calc come from large
>> Zn2+--ZBG(ZN-bonded-group) electrostatics interaction.
>> (in no-bonded model, charge was set as 2+, while in bonded model from
>> other paper, charge on ZN is ~0.95 or 1)
>> (3) what should be modified in my MM_PBSA calculation with current
>> no-bonded model?
>>
>> {{I am using amber7 and no-bonded model with 2+ charge on metal ions.
>> MD simulations were run for 500ps, from ~200ps-500ps, the complex
>> system reach equlibrium stage. I also analyzed Zn-His distance and
>> some other H-bonds, and found that this complex system is well stable
>> with Zn-His coordinate and stable H-BOND between ligand and protein.
>> I take 100 snapshots from 300-500ps traj for MM_PBSA calculation.}}
>>
>> Any reply would be very appreciated!
>>
>> Best regard!
>>
>> Yong Xu
>> yxu_at_mail.sioc.ac.cn
>> 2005-04-13
>>
>> ===========================================================
>> * Yong Xu
>> * State Key Lab of Bioorganic & Natural Product Chemistry
>> * Shanghai Institute of Organic Chemistry
>> * Chinese Academy of Science
>>
>> * 354 Feng Lin Road, Xu Hui District
>> * Shanghai, 200032, China
>>
>> * Email: yxu_at_mail.sioc.ac.cn
>> * xuyongch_at_yahoo.com
>> ===========================================================
>>
>>
>>
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>
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= = = = = = = = = = = = = = = = = = = =
                        

Best regards!
                                 
　　　　　　　　Yong Xu
　　　　　　　　yxu_at_mail.sioc.ac.cn
　　　　　　　　　　2005-04-13
===========================================================
* Yong Xu
* State Key Lab of Bioorganic & Natural Product Chemistry
* Shanghai Institute of Organic Chemistry
* Chinese Academy of Science
           
* 354 Feng Lin Road, Xu Hui District
* Shanghai, 200032, China
        
* Email: yxu_at_mail.sioc.ac.cn
* yxuemail_at_sina.com
===========================================================
　　　　　　

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