Question:
Abl (named after a transforming gene of Abelson mouse leukaemia virus) kinase is an important drug target in chronic myeloid leukaemia. In this project examine the amino acid sequences of Abl kinases and consider the problem of development of drug resistance to Imatinib.
Crystal structure of the T315I mutant of Abl kinase. Zhou T, Parillon L, Li F, Wang Y, Keats J, Lamore S, Xu Q, Shakespeare W, Dalgarno D, Zhu X. ChemBiol Drug Des. 2007 Sep;70(3):171-81
Instructions:
Using suitable bioinformatics tools (e.g. BLAST search, Multiple Sequence Alignment, Structural Alignment) investigate your allocated topic and write a report (maximum 1800 words) describing what you have discovered.. The report should be structured as follows:
Abstract: provide a 150 word abstract of your report.
Introduction: describe briefly the background to the topic and explain why this topic may be important.
Methods: describe the methods you have used, taking care to include accurate URL locators, PDB codes and database accession numbers where appropriate.
Results: present the results of your investigation in a logical manner, using figures and tables where appropriate to illustrate and summarise what you have found.
Discussion: give a brief overview of the main findings and discuss these in relation to what is already published in the literature. Include comment on any limitations in the methods you have used and suggest further investigations or experiments that would be useful in the future.
Here is websites you need to use:
Integrated systems (interconnected data bases)
• Gquery (USA)
• UniProt (Europe)
Blast (basic local alignment search tool)
• EBI (European time zone) WUBLAST, BLAST2.0
• NCBI (USA time zone) BLAST2.0 nucleotide orprotein ,
Multiple sequence alignment
• Clustal Omega (you will also need Boxshade for printouts) (Alternative)
• Multalin
Sequence Analysis
• FingerPrints (Motifs, Regular Expressions via DbBrowser)
• ProDom (Domains, Pattern Recognition from Alignments)
• PFAM (Domains and Motif, Pattern Recognition from Hidden Markov Models)
• SMART (Collection of functional domains)
• Scansite (concensus protein-protein interaction sequences)
• PhosphoELM (phosphorylation sites)
• NetPhorest (Phosphorylation sites and kinases)
• NetworKIN (Phosphorylation sites and kinases)
• Gene Cards (Details of gene and gene product function)
Structural Analysis
Existing structure
• PDB (The Protein Structure Database)
• RasMol commands
Predicting structure
• Swissmodel (using structures of related proteins
• PsiPRED (predicting secondary structure)
• JPRED3 (predicting secondary structure)
• Kyte-Doolittle (predicting transmembrane domains)
Background
• Aminoacids
• CATH (Protein structure families)
• EBI (Many other programmes and packages)
• Signalling domain briefings – Pawson
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