Molecular Models on Bioinformatics II - Notes | BIOL 4550, Study notes of Biology

Download Molecular Models on Bioinformatics II - Notes | BIOL 4550 and more Study notes Biology in PDF only on Docsity! Bioinformatics 2: Molecular Modeling Intro to protein and amino acid structure Purpose of the course • Learn the theory and application of modeling methods. • Understand the successes, failures, limitations and shortcomings of modeling algorithms. • Recognize a good versus a bad model and know how to fix errors. • Draw biological conclusions from molecular models. • Design experiments based on modeling. What a protein looks like MSAIQASWPSGTECIAKYNFHGTAEQDLPFC KGDVLTIVAVTKDPNWYKAKNKVGREGIIPA NYVQKREGV Evolutionary models (i.e. alignment) consider a protein to be a string of characters, similar to DNA. Why? Because evolution happens at the DNA level. Because of simplicity. Because in theory this is all the information you need to make a protein. What a protein really looks like Proteins fold into compact, solvent- excluded globules (mostly). Most atoms are highly ordered, some are flexible (disordered). Proteins can be completely solvated or they can be embedded in a membrane. Proteins may contain ligands or covalent modifications. ...or if you prefer ball-and-stick model,showing covalent bonds backbone trace, colored from N- terminus to C- terminus cartoon,showing secondary structure Hydrogen bonds donor acceptor H δ- δ+ δ- Must be electronegative atoms: N or O Acceptor must have a free electron pair. : Hydrogen bonds are a linear arrangement of three atoms, two electronegative (O or N) and an electropositive hydrogen in the middle. The atoms are closer together than expected for a “non- bonded” interaction, but not close enough for a covalent interaction. Typical backbone H-bond C N O C C H H C N O C CN H HH H These atoms are arranged in a line, approximately. H-bonds between backbone atoms define secondary structure. Alpha helix Right-handed helix. H-bond is from the oxygen at i to the nitrogen at i+4. α- helices have an overall dipole because the H-bonds are all in the same direction. + Helices are not as “cylindrical” as the cartoon suggests. Sidechains ACDEFGHIKLMNPQRSTVWY There are 20 natural amino acids (meaning those recognized by tRNA-synthetases) [some say seleno- cysteine is also a natural amino acid. I don’t know] These chemical nature of these 20 sidechains account for the folding and function of proteins. Memorize them! Cartesian coordinates have an implied reference frame ATOM 1 N VAL 1 0.616 -1.613 20.826 1.00 68.81 8DFR 152 ATOM 2 CA VAL 1 0.737 -1.197 19.414 1.00 65.36 8DFR 153 ATOM 3 C VAL 1 0.597 -2.511 18.644 1.00 62.65 8DFR 154 ATOM 4 O VAL 1 1.207 -3.526 18.989 1.00 65.13 8DFR 155 ATOM 5 CB VAL 1 1.994 -0.410 19.048 1.00 67.55 8DFR 156 ATOM 6 CG1 VAL 1 2.452 0.572 20.132 1.00 68.01 8DFR 157 ATOM 7 CG2 VAL 1 3.154 -1.279 18.586 1.00 66.94 8DFR 158 X Y Z Å = angstroms = 10-10 m 1Å = 0.1 nm X Y Z Coordinates are relative to a “reference frame” X-ray crystallography solves structures in Cartesian coordinates Internal coordinates are independent of reference frame •Internal coordinates model the covalent structure of the molecule. •Components: •bond lengths •bond angles •torsion (dihedral) angles •planar groups •pairwise distances NMR structures are solved in Internal Coordinates C C1.54Å C C C 109° C=O C=O In class “exercise”: Make a right-handed 60° torsion angle using a paperclip. Compare with your neighbor by superposition. Are they superimposable? If your paperclip was the alanine backbone, where would Cβ be? N φ=+60° CαC C O Cβ C=O O C=O Cβ Q: Is φ=-60 more, or less, stable than φ=+60°, for ALA? What about for GLY? Converting internal coordinates t Cartesian. These two molecules have identical torsion angles, and only slight differences in backbone bond lengths and bond angles. Errors accumulate! Rasmol: How to select one amino acid To open file xxxx.pdb in Rasmol type: % rasmol xxxx.pdb In RasMol: (rasmol prompt is “”) restrict ala (or any amino acid, 3 letter code) Click on one of the displayed residues restrict nnn (where nnn is the residue number) To return to whole protein: select protein wireframe 100 (or select Display->sticks) Drawing amino acids • Draw using approximately correct bond angles. • Draw only polar hydrogens (H-bond donors) • Draw a “:” at each H-bond acceptor • Circle each chiral center. • Draw a rotating arrow around each rotatable bond. • Rank the amino acids from polar to non-polar and small to large. Drawing tryptophane C C C C C CC C C N C C N O H H :