Chemoinformatics

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Chemoinformatics And Bioinformatics
Cédric Notredame
Molecular Biology
Bioinformatics
Chemoinformatics
Chemistry
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Bioinformatics and Chemoinformatics
Scale
Chemoinformatics
Bioinformatics
Sequences ----------(Structures)-----------Ligands
/Lead
Genes Genomes
Drugs
Proteins
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Bioinformatics and Chemoinformatics
Describing the DATA
Chemoinformatics
Bioinformatics
Sequences -----------(Structures)-----------Ligand
s
Each Atom
ChainAtom
Chain
AGCTGTCGAGGGATAGGACA TATACATAAATTAATATAAT
SMILES, Sybyl, Matrices Structure Descriptors
Strings
3D-Structure
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Bioinformatics and Chemoinformatics
Storing the DATA
Chemoinformatics
Bioinformatics
Each Atom
ChainAtom
Chain
SMILES, Sybyl, Matrices, descriptors
AGCTGTCGAGGGATAGGACA TATACATAAATTAATATAAT
Strings
3D-Structure
Chemical Structure
Coordinates
Sequence
GenBank Genomes
CAPLUSREGISTRY
PDB
Genpep/NR proteins
SwissProt
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Related Techniques Databases
Bioinformatics NCBI/EBI
Chemoinformatics CAS/Beilstein/MDL
Finding the right Database is NOT an issue as
most data are public.
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Bioinformatics and Chemoinformatics
Comparing the DATA
Chemoinformatics
Bioinformatics
Sequences -----------(Structures)-----------Ligand
s
Fold
Similarity
Descriptor
Evolutionary model
Descriptor Similarity
3D-Model
Structure/StructureComparison
Backtracking Algorithm
Dynamic Programming
LSQman DALI SAP
CACTUS (Cactus.nci.nih.gov)
BLAST
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Related Techniques Searching Databases
Bioinformatics Dynamic Programming
Chemoinformatics Backtracking
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Bioinformatics and Chemoinformatics
Building Models
Chemoinformatics
Bioinformatics
Sequences -----------(Structures)-----------Ligand
s
Fold
MSA
Descriptor
Multiple Sequence Alignments ClustalW, TCoffee
Descriptor Computation
3D-Model Classifications
DALI SCOP CAT
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Related Techniques Profiles
Bioinformatics
Chemoinformatics
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Bioinformatics and Chemoinformatics
Predicting Properties
Chemoinformatics
Bioinformatics
Sequences -----------(Structures)-----------Ligand
s
Binding
Function
Descriptor
QSAR
Docking/Mecanisms
Multiple Comparisons
Profiles Pfam
Relate descriptors to
Molecular Dynamic Docking Predictions
Function
Structure
Activity/Toxicity
Phylogeny
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Related Techniques Profiles and Descriptors
Bioinformatics
Chemoinformatics
Pharmacophore
Database Search With a Profile
Database Search With a Profile
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Bioinformatics/ Chemoinformatics Each One in
its Niche
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Bioinformatics and Chemoinformatics The Questions
Bioinformatics Target
Chemoinformatics Lead
Compound Database
Target
Site
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Bioinformatics and Chemoinformatics The Questions
Evolutionary Trace
Chemical Modelling
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Bioinformatics and Chemoinformatics The Questions
Bioinformatics Function
Chemoinformatics QSAR
Quantitative Structure-Activity Relationship
Comparative Genomics
Function
Activity/Toxicity
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Bioinformatics and Chemoinformatics The Questions
Bioinformatics Target
Chemoinformatics Lead
2D/3D QSAR Molecular Dynamic
Comparative Genomics Molecular Dynamic
Docking
In Silico Screening
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Bioinformatics and Chemoinformatics The Algorithms
Bioinformatics Target
Chemoinformatics Lead
Graph Theory
Neural Networks
Genetic Algorithms
Dynamic Programming
Backtrace
Hidden Markov Models
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Bioinformatics/ Chemoinformatics Where Do They
Meet
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Homology based SAR predictions
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Homology based SAR predictions

• SAR Matrices contain affinity Data

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Homology based SAR predictions

• Targets can be clustered from the SAR Data

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Homology based SAR predictions

• Targets can be clustered using similarity

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Homology based SAR predictions

• Sequence Clustering Can be done using Key
  positions

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Homology based SAR predictions

• Sequence Clustering Can be done using Key
  positions

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Homology based SAR predictions

• Does it Work ???
• Clustering Based on Active Site Residues

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Homology based SAR predictions

• Pairs of Comparable Kinases

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Bioinformatics/ Chemoinformatics Main
Differences ?
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Bioinformatics and Chemoinformatics
Chemoinformatics
Bioinformatics
Small Molecules
Macro-molecules
Chemical Modelling
Evolutionary Signal