Molecular dynamics of two ester hydrolases: comparison using the BioSimGrid database Kaihsu Tai.

Molecular dynamics of two ester

hydrolases: comparison using the

BioSimGrid database

Kaihsu Tai

The systems

● both serine esterases (ester hydrolases, EC 3.1.1)

● with the catalytic triad: Ser - His - Glu|Asn

OMPLA AChE

N156

H142

S144

E334

H447

S203

The trajectoriestrajectory description time/ns id code

Apo-AChE unliganded monomer 15 GB-OXF_11

Fas-AChE liganded with fasciculin 2 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

● ...not yet data deluge

● but...

articles with “molecular dynamics” in

title or abstract in the Biophysical

Journal

(one of the first protein MD: 1980 McCammon et al.)

year number

2004 (up to November) ~97

2003 ~96

2002 ~70

2001 ~55

2000 ~471995 to 1999 ~186

1990 to 1994 ~48

1976 to 1989 <25

Things we tried that did not work

very well● 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

● Here we had some intuition, and formed a model.

– Is it possible to do model-free data mining?

– n × n rmsd (as Bing may have shown), etc.

– Yes, we can do it, but what is the

biological/biochemical relevance?

● The answer is 42 - what is the question?