Introducing cavities in the core by mutations such as

Info icon This preview shows pages 36–50. Sign up to view the full content.

View Full Document Right Arrow Icon
-introducing cavities in the core by mutations such as Ile Val or Phe Leu Cavity for a CH2 Stability by 1kcal/mol -More delicate design -Needs structure
Image of page 36

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full Document Right Arrow Icon
Prediction of Structure From Sequence Empirical – in progress ~70% successful-at best (62-65%) Essence: Pattern Recognition Key: Evolutionary Information Sequence homology implies similarity in structure and function By inference/By Anaysis Data bases (2007 >500,000 seq., >45,000 Structures Information Prediction Example: Homologous proteins Conserved Core Variable Loop
Image of page 37
Secondary Structure Prediction for 3-Model Predict: α, β, loop, β-turn Predict: membrane-spanning α-helix Predict: Amphipatic structures α β Prediction of the folded structure of tryptophan synthetase, and the catalytic subunit of c-AMP dependent protein kinase
Image of page 38

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full Document Right Arrow Icon
Chou & Fassman (1974) Frequency of occurrence of a given a.a. in α, β, and loops in all protein structures in the database (statistical) Nearest neighbors output: probability for each residue to be in α, β, or Loop Artificial intelligence/neural networks Train a computer to recognize patterns – the more information and the “more practice” the higher the accuracy (in progress)
Image of page 39
Design • Minibody • Chymohelizyme Calcium channel
Image of page 40

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full Document Right Arrow Icon
Minibody Synthetic (61 a.a.) All β Template: heavy chain, variable domain of IgG Hypervariable loops Binding site: Histidines in each hypervariable loop • Protein it folds and in binds metal (Zn +2 )
Image of page 41
Chymohelizyme (Science 248: 1544, 1990) Design (computer based): 4 helices, parallel, amphipathic, serine protease Catalytic TRIAD Ser, His, Asp at the N-end of the bundle in the same spatial arrangement as chymotrypsin “oxyanion hole” and substrate binding pocket for acetyl tyrosine ethyl ester, a classical substrate of CT were included in the design Synthetic enzyme is catalytically active and inhibitor-specific
Image of page 42

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full Document Right Arrow Icon
Image of page 43
Image of page 44

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full Document Right Arrow Icon
Image of page 45
Image of page 46

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full Document Right Arrow Icon
Image of page 47
Image of page 48

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full Document Right Arrow Icon
Image of page 49
Image of page 50
This is the end of the preview. Sign up to access the rest of the document.

{[ snackBarMessage ]}

What students are saying

  • Left Quote Icon

    As a current student on this bumpy collegiate pathway, I stumbled upon Course Hero, where I can find study resources for nearly all my courses, get online help from tutors 24/7, and even share my old projects, papers, and lecture notes with other students.

    Student Picture

    Kiran Temple University Fox School of Business ‘17, Course Hero Intern

  • Left Quote Icon

    I cannot even describe how much Course Hero helped me this summer. It’s truly become something I can always rely on and help me. In the end, I was not only able to survive summer classes, but I was able to thrive thanks to Course Hero.

    Student Picture

    Dana University of Pennsylvania ‘17, Course Hero Intern

  • Left Quote Icon

    The ability to access any university’s resources through Course Hero proved invaluable in my case. I was behind on Tulane coursework and actually used UCLA’s materials to help me move forward and get everything together on time.

    Student Picture

    Jill Tulane University ‘16, Course Hero Intern