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.mail.sioc.ac.cn
2005-04-13
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* 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.mail.sioc.ac.cn
* xuyongch.yahoo.com
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Received on Wed Apr 13 2005 - 02:53:00 PDT
