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Printable Handouts
Navigable Slide Index
- Introduction
- Libraries of de novo amino acid sequences
- Designed libraries of folded proteins
- Amphipathic alpha helix and beta strand
- Binary patterned 4-helix bundle
- Suggested sequence for alpha-helix
- Genetic code for the suggested sequence
- Rational design and combinatorial approach
- Cloning the library into E.coli
- Example of several sequences from the library
- Combinatorial libraries of sequences
- Well folded "native-like" structures
- Most of the proteins were molten globules
- Design: 74 amino acid, 14 residues/helix
- The first and the second generation libraries
- Stability of the 1st and 2nd generation libraries
- NOESY spectra
- NMR for proteins from the unselected library
- Experimentally determent structure
- Superposition of low energy structures
- Polar/nonpolar periodicity of de novo 4-helix bundle
- Sequence of S-824
- Functional proteins in unselected binary libraries
- Heme binding
- Functions of heme proteins
- Peroxidase reaction
- Screen for peroxidase activity
- Peroxidase activity by oxidation of ABTs
- Catalysis without cofactors?
- Hydrolysis of p-nitrophenyl acetate by S-824
- Esterase activity kcat/kuncat = 8700
- A binary code for protein design
- Binary patterning of alpha-helix and beta strand
- A designed beta sheet template
- Binary patterned beta-sheet sequences
- Alpha-helix versus beta-sheet
- De novo beta-sheet proteins
- Binary patterns in natural sequences
- Engineering monomeric beta-sheet proteins
- Chromatography and circular dichroism
- Summary for binary code for protein design
- Biomaterials
- Binary patterned design for beta-sheet proteins
- Model of graphite surface and AFM image
- Acknowledges
Topics Covered
- Novel proteins can be devised using either rational/computational approaches or random/combinatorial methods
- Description of a hybrid approach that combines rational and combinatorial methods: libraries of novel proteins
- Combinatorial diversity
- Random vs. focused libraries
- Amphiphilic alpha-helices and beta-strands
- Binary patterning of polar and non-polar amino acids
- Genetic encoding of combinatorial mixtures of polar and non-polar amino acids
- Design of libraries of novel 4-helix bundles
- Library construction and expression in vivo
- Dynamic vs. wellordered protein structures
- Second generation libraries
- Biophysical characterization
- Solution structure of native-like 4-helix bundle proteins from designed libraries
- Functionally active proteins including cofactor binding proteins, peroxidases and esterases
- Designed libraries of beta sheet proteins: amyloid-like fibrils, monomeric beta-sheet proteins and novel biomaterials
Talk Citation
Hecht, M. (2007, October 1). Novel proteins from designed combinatorial libraries [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved October 5, 2024, from https://doi.org/10.69645/UTMA5950.Export Citation (RIS)
Publication History
Financial Disclosures
- Prof. Michael Hecht has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.