AMBER Archive (2005)

Subject: RE: AMBER: Is the MD simulation normal

From: Yong Duan (duan_at_ucdavis.edu)
Date: Fri May 27 2005 - 11:31:27 CDT

Shulin,

MD simulation is a way of doing stat-mech on computer. This means,
things you observe in one trajectory are just from one trajectory. This
is quite different from, say, QM calculations where you focus on
energetics. Here, your observations are two of (many) probablistic
events. Your observation and conclusion, depends very much on the luck.
Anyway, to fully appreciate what I am saying, you need to understand a
little bit about the stat-mech. In other words, you were relatively
lucky in the first simulation and were not as lucky in the second.

As for 2.33mM vs 7uM, you are right that one should expect that 7uM is
more stable than 2.33mM. Without knowing the detail of the 2.33mM,
whatever I say here is speculative. Therefore, I stop making any further
comment.

Another thing that you should keep in mind is that the binding affinity
is related to DG. Which means, it is the free energy difference of two
states, solution state vs holo state.

My suggestion to you is to do more analyses and make the judgement by
yourself (with your advisor). As far as the information is concerned,
nothing went wrong with the simulation.

yong

-----Original Message-----
From: owner-amber_at_scripps.edu [mailto:owner-amber_at_scripps.edu] On Behalf
Of Shulin Zhuang
Sent: Friday, May 27, 2005 12:38 AM
To: amber_at_scripps.edu
Subject: Re: AMBER: Is the MD simulation normal

Dear Prof. Duan,

I have ever MD of one inhibitor with a Ki of only 2.33mM, but all goes
well, what's more the the inhibitor binds to the same protein with the
disccussed inhibitor that has IC50 of 7uM. The big difference is that,
the former inhibitor is very rigid and the later is relatively flexable
and has 30 atoms.

according to your advice, I get the B-factor of the inhibitor, B-factors
of several atoms are too big. Does it means that the results are normal
and I need not to continue to run the MD?

Please see the following data:

Atom no B-factor

1 4.8025
2 32.48008
3 27.58063
4 28.61952
5 2.31655
6 2.37586
7 11.6511
8 2.62466
9 4.47218
10 7.26247
11 2.72919
12 4.15794
13 6.45167
14 6.92309
15 4.71467
16 5.09964
17 3.57848
18 2.85317
19 1.01439
20 1.39801
21 3.13097
22 2.43842
23 5.56094
24 2.49007
25 7.00789
26 10.12751
27 1.14021
28 2.71137
29 0.81603
30 2.5196

best regards
shulin

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