MTech Insilico Protein Engineering & Design syllabus for 2 Sem 2020 scheme 20BBI242

Introduction to Proteins:

Amino acids (three and single letter codes) and their molecular properties (size, solubility, charge, pKa), Chemical reactivity in relation to posttranslational modification (involving amino, carboxyl, hydroxyl, thiol, imidazole groups) and peptide synthesis. Primary structure: peptide mapping, peptide sequencing - automated Edman method and Mass Spectrometry. High-throughput protein sequencing. Methods of protein isolation, purification and quantification, and functional analysis.

Higher order structures:

Alpha, beta and loop structures and methods to determine Supersecondary structure: Alpha-turn-alpha, beta-turn beta(hairpin), beta-sheets, alpha-beta-alpha, topology diagrams, TIM barrel structures, nucleotide binding folds. Tertiary structure: Domains, denaturation and renaturation, protein folding pathways, overview of methods to determine 3D structures, Interaction with electromagnetic radiation (radio, micro, infrared, visible, ultraviolet, Xray) and elucidation of protein structure. Quaternary associations: Modular nature, formation of complexes.

Protein Structures:

PDB, structure based classification, databases, visualization tools, structure alignment, domain architecture databases, protein-ligand interactions. Covalent, Ionic, Hydrogen, Coordinate, hydrophobic and Vander walls interactions in protein structure. Bioinformatics Approaches: Secondary structure prediction and determination of motifs, profiles, patterns, fingerprints, super secondary structures, prediction of substrate binding sites, tertiary structure, quaternary structure, methods to determine tertiary and quaternary structure, posttranslational modifications.

Protein databases:

Analysis, computational methods to alter primary structure of proteins, examples of engineered proteins, protein design, principles and examples. Advantages and purpose, overview of methods, underlying principles with specific examples: thermal stability T4-lysozyme, de novo protein design. Case studies of DNA-binding proteins, transcription factors, Helix-turnHelix motif, Zn fingers, helix-turn helix motifs in homeodomain, Leucine zippers,

Case Studies:

Membrane proteins: engineering of Transmembrane segments, prediction, analysis of bacteriorhodopsin and Photosynthetic reaction center. Engineering antibodies. Case studies on Abzymes and Enzymes: Serine proteases, understanding catalytic design by engineering trypsin, chymotrypsin and elastase, substrate assisted catalysis other commercial applications. Peptide design, computational design of peptide therapeutics, peptide drugs, design of synthetic peptides.

Course outcomes:

At the end of the course the student will be able to:

• Understand the basics of protein structures, functional units, architectures and topologies
• Understand the methods of isolation, purification and characterization of proteins
• Apply the principles towards selective modification of proteins strictures and functions
• Understand the Computational aspects of protein engineering and design, with specific case studies.

Question paper pattern:

The SEE question paper will be set for 100 marks and the marks scored will be proportionately reduced to 60.

• The question paper will have ten full questions carrying equal marks.
• Each full question is for 20 marks.
• There will be two full questions (with a maximum of four sub questions) from each module.
• Each full question will have sub question covering all the topics under a module.
• The students will have to answer five full questions, selecting one full question from each module.

Textbook/ Textbooks

1 Protein Engineering Moody P.C.E and A.J Wilkinson IRL Press, Oxford University Press 1991

2 Introduction of protein structure Branden C and Tooze R Garland 1998

Reference Books

1 Bioinformatics Methods & Applications: Genomics, Proteomics & Drug Discovery S, C Rastogi, N Mendiratta& P Rastogi PHI 2013

2 Protein engineering: principles and practice, Jeffrey L. Cleland, Charles S. Craik Wiley-Liss, 1996

3 Introduction to Protein Science. Architecture, Function, and Genomics Arthur M Lesk, Oxford university Press 2016