Protein Structure Prediction Dr. G.P.S. Raghava Protein Sequence + Structure

Protein Structure Prediction Experimental Techniques –X-ray Crystallography –NMR Limitations of Current Experimental Techniques –Protein DataBank (PDB) -> protein structures –SwissProt -> 100,000 proteins –Non-Redudant (NR) -> 10,00,000 proteins Importance of Structure Prediction –Fill gap between known sequence and structures –Protein Engg. To alter function of a protein –Rational Drug Design

Different Levels of Protein Structure

Protein Architecture Proteins consist of amino acids linked by peptide bonds Each amino acid consists of: –a central carbon atom –an amino group –a carboxyl group and –a side chain Differences in side chains distinguish the various amino acids

Amino Acid Side Chains Vary in: Size Shape Polarity

Peptide Bond

Peptide Bonds

Dihedral Angles

Conformation Flexibility Backbone (main chain of atoms in peptide bonds, minus side chains) conformation: –Torsion or rotation angles around: C-N bond (  ) C-C bond (  ) –Sterical hinderance: Most – Pro Least - Gly

Protein Secondary Structure Secondary Structure Regular Secondary Structure (  -helices,  - sheets) Irregular Secondary Structure (Tight turns, Random coils, bulges)

Secondary Structure: Helices H-bond Individual Amino acid ALPHA HELIX : a result of H-bonding between every fourth peptide bond (via amino and carbonyl groups) along the length of the polypeptide chain

Helix formation is local THYROID hormone receptor (2nll)

Secondary Structure: Beta Sheets BETA PLEATED SHEET: a result of H-bonding between polypeptide chains

 -sheet formation is NOT local

Secondary Structure shortcuts

Tertiary Structure: Hexokinase (6000 atoms, 48 kD, 457 amino acids) polypeptides with a tertiary level of structure are usually referred to as globular proteins, since their shape is irregular and globular in form

Quarternary Structure: Haemoglobin