Transcript Molecular dynamics of two ester hydrolases: comparison using the

Molecular dynamics of two ester
hydrolases: comparison using the
BioSimGrid database
Kaihsu Tai
The systems
H142
N156
S144
S203
H447
OMPLA
E334
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both serine esterases (ester hydrolases, EC 3.1.1)
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with the catalytic triad: Ser - His - Glu|Asn
AChE
The trajectories
trajectory
description
Apo-AChE unliganded monomer
Fas-AChE liganded with fasciculin 2
time/ns
id code
15 GB-OXF_11
5 GB-OXF_12
OMPLA1
unliganded monomer, Ewald
10 GB-OXF_16
OMPLA2
unliganded dimer, Ewald
10 GB-OXF_17
OMPLA3
liganded dimer, Ewald
10 GB-OXF_15
OMPLA4
unliganded monomer, cutoff
5.7 GB-OXF_9
OMPLA5
unliganded dimer, cutoff
5 GB-OXF_10
OMPLA6
liganded dimer, cutoff
5 GB-OXF_14
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...not yet data deluge
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but...
articles with “molecular dynamics” in
title or abstract in the Biophysical
Journal
year
2004 (up to November)
2003
2002
2001
2000
1995 to 1999
1990 to 1994
1976 to 1989
number
~97
~96
~70
~55
~47
~186
~48
<25
(one of the first protein MD: 1980 McCammon et al.)
Things we tried that did not work
very well
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Picking candidate atoms from the side chain of
the triad and generate
–
the meta-plot
–
the meta-histogram
Meta-plot
Meta-histogram
A set of metrics for triad intactness
A set of metrics for triad intactness
Looking ahead
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Here we had some intuition, and formed a model.
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Is it possible to do model-free data mining?
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n × n rmsd (as Bing may have shown), etc.
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Yes, we can do it, but what is the
biological/biochemical relevance?
The answer is 42 - what is the question?