Protein Structural Prediction Protein Structure is Hierarchical Structure Determines Function The Protein Folding Problem What determines structure? Energy Kinematics How can we determine structure? Experimental methods Computational predictions Primary Structure: Sequence
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The Protein Folding Problem
A useful mnemonic for the hydrophobic amino acids is "FAMILY VW"
Fauchere and Pilska (1983). Eur. J. Med. Chem. 18, 369-75.
Experimentally Determined Hydrophobicity Levels
(The Holy Grail)
Sequence implies structure, therefore in principle we can predict the structure from the sequence alone
Abundance of alanine at all positions
Non-polar side chains favored at positions 3, 6, 10 (methionine, leucine, isoleucine)I-Sites Examples
Structural Classification Of Proteins
FAMILY: proteins that are >30% similar, or >15% similar and have similar known structure/function
SUPERFAMILY: proteins whose families have some sequence and function/structure similarity suggesting a common evolutionary origin
COMMON FOLD: superfamilies that have same secondary structures in same arrangement, probably resulting by physics and chemistry
CLASS: alpha, beta, alpha–beta, alpha+beta, multidomain
SCOP: Structural Classification of Proteins. 1.67 release24037 PDB Entries (15 May 2004). 65122 Domains.
Chothia, Gough, Vogel, Teichmann, Science 300:1701-17-3, 2003
Evolution of proteins happens mainly through duplication, recombination, and divergence
The number of unique structural folds
is small (possibly a few thousand)
90% of new structures submitted to PDB in the
past three years have similar folds in PDB