hello Dr. Case, As per your suggestion (please see email below), I ran the
nmode calculations separately for 5 different snapshots instead of using the
mm_pbsa-nmode script, in the hope of getting better/lower STD.
The results from the initial nmode calculation was:
# COMPLEX RECEPTOR LIGAND
# ----------------------- -----------------------
-----------------------
# MEAN STD MEAN STD
MEAN STD
# ======================= =======================
=======================
TSTRA 17.47 0.00 17.46 0.00 13.89
0.00
TSROT 17.83 0.01 17.81 0.00 12.00
0.01
TSVIB 2778.59 12.75 2721.74 13.33 47.17
1.63
TSTOT 2813.90 12.75 2757.01 13.33 73.06
1.63
# DELTA
# -----------------------
# MEAN STD
# =======================
TSTRA - 13.87 0.00
TSROT -11.98 0.02
TSVIB 9.69 16.63
TSTOT -16.17 16.64
~
In an attempt to lower the STD, post-calculation results of the individual
snapshots are as follows; ofcourse, I converted the S(cal/mol-K) reported in
the nmode.out to Kcal/mol and made the following table for the 6 individual
snapshots:
Complex(TStotal)
STD
Receptor
STD
Ligand
STD
T deltaS
STD
2843.482
9.158574
2795.477
7.9831
69.56
0
-24.37
6.521333
2825.911
2783.296
69.56
-36.13
2816.364
2782.934
69.56
-26.94
2823.572
2778.389
69.56
-21.55
2830.805
2784.739
69.56
-23.49
2824.158
2771.2
69.56
-16.6
mean
2827.382
2782.673
69.56
-24.84667
I checked the nmode output file for all of them, the first 6 modes are all
close to 0. I visualized the eigenvectors in IED plugin of VMD, nothing
seems abnormal (either the receptor alone or the complex). If I run the
nmode calculation using mm_pbsa, the standard deviation is high due to the
contribution of TSVIB only, whereas on performing the individual
calculations, the result is not the same, I am very confused, since I am
using the same snapshots for both the calculations.
Also, although I can lower the STD of NM by this method from about 16 to 6,
the overall deltaG(bind) still remains to be positive, i.e my TdeltaS is
always a higher negative number if not almost equal to the PBtotal value for
all the different ligand-protein complex systems.....any ideas why? From
experimental results, I know the inhibitors binds in the nanomolar range.
I ran the simulation of the solvated system for 5ns (about 3700 atoms w/o
water). The protein has a Ca2+ ion and a bound uncharged inhibitor. 200
snapshots from the last 2ns were used for MM_pbsa, whereas the last 6 frames
were used for nmode calculation. Please let me know what kind of details
about the system might help you in making a judgement.
Any suggestion would help a lot....
Thanks
Rima
On 2/17/07, David A. Case <case.scripps.edu> wrote:
>
> On Sat, Feb 17, 2007, Rima Chaudhuri wrote:
>
> > I looked at the structure in vmd and nothing looks weird
> > post-simulation, hence I doubt if there is an outlier.
>
> I think you need to look at the nmode outputs themselves, study the
> distribution of low-frequency eigenvalues, and see if you can spot
> anything.
> Not knowing anything about your system, I can't say from my vantage point
> what might be happening. Of course, what you see could be real, as well.
>
> ...dac
>
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--
-Rima
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Received on Sun Mar 04 2007 - 06:07:15 PST
