Paulino Gomez-Puertas Bioinformática. 2007 BIOINFORMÁTICA. FARMACOLOGÍA Y TOXICOLOGÍA MOLECULAR- UAM. 2007-2008 http://novacripta.cbm.uam.es/bioweb/courses/Farmamol07 usuario: provisional passwd: bender conectarse a: AULAS [windows]
Paulino Gomez-PuertasBioinformática.2007
BIOINFORMÁTICA.FARMACOLOGÍA Y TOXICOLOGÍA MOLECULAR- UAM.
2007-2008
http://novacripta.cbm.uam.es/bioweb/courses/Farmamol07
usuario: provisional passwd: bender conectarse a: AULAS
[windows]
Paulino Gomez-PuertasBioinformática.2007
BIOINFORMÁTICA.FARMACOLOGÍA Y TOXICOLOGÍA MOLECULAR- UAM.
2007-2008
10 Octubre - 14 Diciembre de 2007.
Profesor:
Paulino Gómez-Puertas (CBMSO)
Paulino Gomez-PuertasBioinformática.2007
Contacto:
Paulino Gómez-Puertas (CBMSO) <[email protected]>
http://www.cbm.uam.es/bioweb
Contenidos del curso:
http://novacripta.cbm.uam.es/bioweb/courses/Farmamol07
Paulino Gomez-PuertasBioinformática.2007
http://novacripta.cbm.uam.es/bioweb/courses/Farmamol07
Paulino Gomez-PuertasBioinformática.2007
Bioinformática.
Introducción
Paulino Gómez Puertas. CBM-SO.
Paulino Gomez-PuertasBioinformática.2007
Bibliografía.
Lesk, A.M. "Introduction to bioinformatics" 2dn Ed., Oxford University Press, 2005.
<http://www.oup.com/uk/orc/bin/9780199277872/>
Claverie, J-M & Notredame, C. "Bioinformatics for Dummies" 2nd. Ed.Wiley Publishing, INC. 2006.
<http://www.dummies.com/WileyCDA/DummiesTitle/productCd-0470089857.html>
Mount, D. " Bioinformatics: Sequence and Genome Analysis". CSHL Press, 2004.
<http://www.cshlpress.com/default.tpl?action=full&cart=114614504783965&--eqskudatarq=465> <http://www.bioinformaticsonline.org/>
Paulino Gomez-PuertasBioinformática.2007
Molecular Modeling Group
Paulino Gómez-PuertasEduardo López-ViñasJesús Mendieta Gómez
Computational analysis of protein-protein and protein-ligand interaction.http://www.cbm.uam.es/bioweb
Paulino Gomez-PuertasBioinformática.2007
Molecular chaperonin GroEL
subunit
heptamer
(Dr Jianpeng Ma, Harvard Univ.)
ATP
Paulino Gomez-PuertasBioinformática.2007
Virtual Docking
Paulino Gomez-PuertasBioinformática.2007
Molecular dynamics simulation.
ab initio methods
Paulino Gomez-PuertasBioinformática.2007
Alain Leppinette. CAB.
Paulino Gomez-PuertasBioinformática.2007
Alain Leppinette. CAB.
Paulino Gomez-PuertasBioinformática.2007
bonding terms
( )20bbonds
bonds bbk21E −= ∑
( )∑ −=angles
20angle k
21E θθθ
( )[ ]∑ −+=dihedrals
0ddihedral cos1k21E θθ
∑=ij ij
ji
0elect r
qq4
1Eεπε
repulsive
atractive
∑ −=−ij
6ij
ij12ij
ijJonesLennard r
BrA
E
non-bonding terms
Molecular Mechanics and Dynamics as tools for research in Biomedicine.
Paulino Gomez-PuertasBioinformática.2007
PROTEIN UNFOLDING
Ribonuclease E. coli
Paulino Gomez-PuertasBioinformática.2007
Paulino Gomez-PuertasBioinformática.2007
PROTEIN UNFOLDING
Ribonuclease E. coli (stable mutant)
Paulino Gomez-PuertasBioinformática.2007
Video "The Inner Life of a Cell":http://www.studiodaily.com/main/searchlist/6850.html
Paulino Gomez-PuertasBioinformática.2007
compoundcollections
receptorstructure
Protein3D model
virtuallibraries
Virtual Screening
computationalscreening
no. compounds
filtering criteria:docking energy
spatialcomplementarity3D simmilarity
profiles
1.000.000
100.000
5.000
250
in vitro screen smaller focused libraries
Paulino Gomez-PuertasBioinformática.2007
acyl-CoA
carnitineacil-carnitine
malonyl-CoA
CARNITINE PALMITOYLTRANSFERASE.
Paulino Gomez-PuertasBioinformática.2007
CPT1A
CPT1BCOT
CPT2CrAT
ChAT
long
cha
in a
cyl-C
oA
short chain acyl-CoA
medium chain acyl-CoA
malonyl-CoA regulated
malonyl-CoA insensitive
choline
carnitine
carnitine/choline acyl transferases
CPT1C
Paulino Gomez-PuertasBioinformática.2007
Malonyl-CoA regulation: Met vs. Ser
Carnitine-Choline: Thr/Glu/Thr vs. Val/Asp/Asn
Short vs. Long substrate: Gly vs. Met
Paulino Gomez-PuertasBioinformática.2007
H1E1E2
E3
E4Ala 9
Arg 52
Structural modeling of human CPT1 enzyme. Influence on enzyme activity.
CPT1 (C-ter)CPT1 (N-ter)
Paulino Gomez-PuertasBioinformática.2007
R45
D698
Malonyl-CoA
E26
K561
malonyl-CoA
CPT1A-RAT 20 46CPT1A-MOUSE 20 46 CPT1A-HUMAN 20 46CPT1B-MOUSE 20 46 CPT1B-RAT 20 46CPT1B-HUMAN 20 46CPT1B-PIG 20 46
E26
K561
CPT1A-RAT 555 575CPT1A-MOUSE 555 575CPT1A-HUMAN 555 575CPT1B-MOUSE 555 575CPT1B-RAT 555 575CPT1B-HUMAN 555 575CPT1B-PIG 555 575
Paulino Gomez-PuertasBioinformática.2007
Modeling of CPT1 interaction toligands and inhibitors
malonyl-CoA
carnitineC75-CoA
C75-CoA
carnitine
H473
Paulino Gomez-PuertasBioinformática.2007
Inner mitochondrial membrane
carnitine palmitoyl-carnitine
CPT2
CoA palmitoyl-CoA
carnitine/acyl-carnitine transporter
Outer mitochondrial membrane
3 CPT1 - transmembrane segments
CoA
palmitoyl-CoA
malonyl-CoA
ACC2 - dimerACBP
CoApalmitoyl-CoA
Acyl-CoA synthetase
CPT1trimer
Next future: 3D modeling of complete CPT system.
Paulino Gomez-PuertasBioinformática.2007
Next future: "in silico" design of new drugs.
Paulino Gomez-PuertasBioinformática.2007
Cuestiones…