Protein structure determination prediction Tertiary protein structure protein
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Protein structure determination & prediction
Tertiary protein structure: protein folding Three main approaches: [1] experimental determination (X-ray crystallography, NMR) [2] Comparative modeling (based on homology) [3] Ab initio (de novo) prediction (Dr. Ingo Ruczinski at JHSPH)
Experimental approaches to protein structure [1] X-ray crystallography -- Used to determine 80% of structures -- Requires high protein concentration -- Requires crystals -- Able to trace amino acid side chains -- Earliest structure solved was myoglobin [2] NMR -- Magnetic field applied to proteins in solution -- Largest structures: 350 amino acids (40 k. D) -- Does not require crystallization
Steps in obtaining a protein structure Target selection Obtain, characterize protein Determine, refine, model the structure Deposit in database
X-ray crystallography http: //en. wikipedia. org/wiki/X-ray_diffraction Sperm Whale Myoglobin
Nuclear magnetic resonance spectroscopy http: //en. wikipedia. org/wiki/Nuclear_magnetic_resonance
Article
Ab initio protein prediction n Starts with an attempt to derive secondary structure from the amino acid sequence Predicting the likelihood that a subsequence will fold into an alpha-helix, beta-sheet, or coil, using physicochemical parameters or HMMs and ANNs ¨ Able to accurately predict 3/4 of all local structures ¨
Secondary structure prediction Chou and Fasman (1974) developed an algorithm based on the frequencies of amino acids found in a helices, b-sheets, and turns. Proline: occurs at turns, but not in a helices. GOR (Garnier, Osguthorpe, Robson): related algorithm Modern algorithms: use multiple sequence alignments and achieve higher success rate (about 70 -75%) Page 279 -280
Fold recognition (structural profiles) Attempts to find the best fit of a raw polypeptide sequence onto a library of known protein folds n A prediction of the secondary structure of the unknown is made and compared with the secondary structure of each member of the library of folds n
Threading n Takes the fold recognition process a step further: ¨ Empirical-energy functions for residue pair interactions are used to mount the unknown onto the putative backbone in the best possible manner
- Protein structure determination
- Primary secondary tertiary quaternary structure
- Primary secondary and tertiary protein structure
- Protein tertiary structure bonds
- Leucine polar or nonpolar
- Primary secondary and tertiary structure of protein
- Structural protein
- Koji tsuda
- X-ray structure determination
- Phd secondary structure prediction
- Rna secondary structure prediction
- Protein structure
- Primary secondary tertiary quaternary
- Tertiary storage
- Primary, secondary tertiary amine
- Tertiary structure
- Protein pump vs protein channel
- Protein-protein docking
- Coefficient of determination formula in regression