Bioinformatics and Protein Modelling: Possible Routes to Drug Discovery


Click here to start

Table of contents

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

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

Structure Error

Conclusions

Author: Andrew C.R. Martin

E-mail: a.c.r.martin@reading.ac.uk

Homepage: http://www.bioinf.org.uk