AMBER Archive (2005)

Subject: Re: AMBER: Is the MD simulation normal

From: Shulin Zhuang (shulin.zhuang_at_gmail.com)
Date: Thu May 26 2005 - 23:23:37 CDT

Dear Prof. Duan and Prof. Cheatham,

Appreciated for your kind answer! According to your valuable advice,
I describe my MD in more detail.

To Prof. Cheatham：
>If you were using constant pressure with restraints (NTR=1), then the
relative >positions of the molecules may change due to pressure
scaling. To get around >this, only restrain the protein and add in
explicit hbond restraints (using the NMR >options) for the
equilibration phase.

 I do not use constant pressure with restraints (NTR=1), but use
constant volume with restraints (NTR=1) to heat up the system.

For the MD details:
Several- stage constraints minimizations were performed first and then
50 ps NVT MD to heat up the system from 0 K to 300k was performed.
During the constraints, I just only let the hydrogen free and at the
NVT MD stage, the constraints force was 5 kcal/mol. After above, the
following 1 ns NPT MD without any constraints was carried out.

To Prof. Duan：
>1) How soon did you loss that hydrogen bond and did it ever go back.

One hydrogen bond lose after 200 ps and another new hydrogen bond
forms; after about 20 ps , another hydrogen bonds was lost and another
new hydrogen bond forms. In a word, two hydrogen bonds were lost and
another two hydrogen bonds forms at the same time stage.
 I have attached several figures. Please examine the attached files.
Take you time.

>2) Is the hydrogen bond exposed to solvent? This can give you clue as to
>
the stability.
The two hydrogen bonds are not exposed to solvent.

>3) It sounds like that your complex is a bit unstable. Any experimental
>data on binding affinity (IC50 or Kd)?

The IC50 is 7 uM, therefore, the inhibitory has a weak binding affinity.

>Keep in mind, hydrogen bonds are weak interactions. Lossing one or two
>is quite common even for stable complex. Hydrogen bonds of 3A or so are
>not considered stable, if that is the distance your system started from.

Two hydrogen bond of my system start from a distance of 2.9 A, 3 A ,
respectively.

best regards
shulin 

-- 
   Shulin Zhuang
Chemistry Department 
Zhejiang University PRC
shulin.zhuang_at_gmail.com
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