Bioinformatics and Protein Modelling: Possible Routes to Drug Discovery
Application of Bioinformatics
But first...
Hydroxyl hydrogen bonding
GRID, Sugars and the Fc fragment
Growth in Data
THE POST-GENOME ERA
THE GENE-TO-DRUG PIPELINE
SELECTING THE BEST TARGETS
Slide 10
STRUCTURE-BASED METHODS FIND MANY NOVEL TARGETS NOT DETECTABLE FROM SEQUENCE SIMILARITY
Slide 12
DHFR as a protozoal drug target
Trypanosomiasis & Leishmaniasis
Dihydrofolate Reductase
Comparative Modelling
Analysis of models and structures
Key differences for Drug design
Drug design
Results
Cautionary Tales
Automated modelling
CATH
Why Compare Alignments?
Alignment Is Critical
Performance in CASP2
Observations
Comparison Method
Methods...
Global Alignment
Local/SS Alignment
Multiple Alignment
Summary of Results
Slippage
Slippage (magnified)
Slippage 0.2 SeqID 70%
Genuine 3hfmH1 vs. 1ay1H1
Genuine 6ldh02 vs. 9ldtA2
Unusual CDR-H3 in 2gfb
Structure Error
Conclusions
Author: Andrew C.R. Martin
E-mail: a.c.r.martin@reading.ac.uk
Homepage: http://www.bioinf.org.uk