This document contains an agenda for bioinformatics lessons covering various topics like biological databases, sequence similarity, sequence alignments, database searching, phylogenetics, protein structure, gene prediction, and bioinformatics applications in drug discovery. It also discusses ongoing bioinformatics research projects and ambitions to publish peer-reviewed work. Finally, it provides background on protein structure, levels of protein structure from primary to tertiary, and experimental methods like X-ray crystallography used to determine protein structures.
8. Rationale for understanding protein structure and function Protein sequence -large numbers of sequences, including whole genomes Protein function - rational drug design and treatment of disease - protein and genetic engineering - build networks to model cellular pathways - study organismal function and evolution ? structure determination structure prediction homology rational mutagenesis biochemical analysis model studies Protein structure - three dimensional - complicated - mediates function
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10. MIS-SENSE MUTATION e.g. Sickle Cell Anaemia Cause : defective haemoglobin due to mutation in β-globin gene Symptoms : severe anaemia and death in homozygote
79. **T112/dhso – 4.9 Å (348 residues; 24%) **T92/yeco – 5.6 Å (104 residues; 12%) **T128/sodm – 1.0 Å (198 residues; 50%) **T125/sp18 – 4.4 Å (137 residues; 24%) **T111/eno – 1.7 Å (430 residues; 51%) **T122/trpa – 2.9 Å (241 residues; 33%) Comparative modelling at CASP CASP4: overall model accuracy ranging from 1 Å to 6 Å for 50-10% sequence identity CASP2 fair ~ 75% ~ 1.0 Å ~ 3.0 Å CASP3 fair ~75% ~ 1.0 Å ~ 2.5 Å CASP4 fair ~75% ~ 1.0 Å ~ 2.0 Å CASP1 poor ~ 50% ~ 3.0 Å > 5.0 Å BC excellent ~ 80% 1.0 Å 2.0 Å alignment side chain short loops longer loops
The new curve saturated around 20% for alignments over more than 250 residues --- and for alignments shorter than 11 residues the new equation yielded values above 100%. However, this was acceptable as 100% identity for gragments of 10-11 residues does not imply structural similarity.