Structural Bioinformatics - Lecture Notes | CS 5890, Study notes of Computer Science

Download Structural Bioinformatics - Lecture Notes | CS 5890 and more Study notes Computer Science in PDF only on Docsity! Struct ural Bioinf or matics CS 5890 Dr. Sean Johnson 07/09/07 Odds and ends... ¢ Strategies for crystallization ¢ Comparing related struct ures We need crystals to solve structures… A crystal isn’t a single molecule, It is millions of copies of the same molecule! Crystals make us happy What do we do when we aren’t happy??? Why don’t crystals grow? Wrong conditions Impure samples Flexible regions Try more (we might try thousands of conditions) Improve purity (not always easy to do) Eliminate flexible regions SER prediction server: nihserver.mbi.ucla.edu/SER/ Surface Entropy Reduction (SER) change flexible side chains on the surface of the protein to something less flexible Need to predict which flexible amino acids are on the surface (look for clusters in predicted loop regions) Looking at structures Visualization is essential • Structure database – Protein data base (PDB) http://www.rcsb.org/ •Model representation (graphics) –Pymol http://pymol.sourceforge.net/ –Rasmol http://www.umass.edu/microbio/rasmol/ –Swiss-PDB Viewer http://www.expasy.ch/spdbv/ ATOM 1 CB MET A 1 -2.605 24.754 111.199 1.00 77.66 A ATOM 2 CG MET A 1 -3.629 24.751 112.310 1.00 80.08 A ATOM 3 SD MET A 1 -3.065 25.642 113.767 1.00 88.70 A ATOM 4 CE MET A 1 -1.302 25.184 113.832 1.00 86.45 A ATOM 5 C MET A 1 -4.017 25.485 109.284 1.00 73.36 A ATOM 6 O MET A 1 -3.539 26.613 109.137 1.00 71.45 A ATOM 7 N MET A 1 -2.085 23.991 108.896 1.00 76.53 A ATOM 8 CA MET A 1 -3.181 24.342 109.847 1.00 75.47 A ATOM 9 N ASP A 2 -5.274 25.176 108.989 1.00 72.29 A ATOM 10 CA ASP A 2 -6.213 26.133 108.421 1.00 71.49 A ATOM 11 CB ASP A 2 -7.567 25.456 108.232 1.00 73.94 A ATOM 12 CG ASP A 2 -7.489 24.254 107.304 1.00 77.48 A ATOM 13 OD1 ASP A 2 -8.542 23.625 107.057 1.00 78.43 A ATOM 14 OD2 ASP A 2 -6.373 23.940 106.823 1.00 77.15 A ATOM 15 C ASP A 2 -6.386 27.426 109.204 1.00 69.04 A ATOM 16 O ASP A 2 -6.390 28.509 108.620 1.00 68.28 A ATOM 17 N SER A 3 -6.534 27.316 110.520 1.00 66.83 A ATOM 18 CA SER A 3 -6.711 28.494 111.367 1.00 63.32 A ATOM 19 CB SER A 3 -6.790 28.076 112.840 1.00 66.03 A ATOM 20 OG SER A 3 -6.040 26.894 113.087 1.00 71.67 A ATOM 21 C SER A 3 -5.621 29.547 111.161 1.00 59.11 A ATOM 22 O SER A 3 -5.907 30.739 111.111 1.00 58.98 A ATOM 23 N ILE A 4 -4.373 29.122 111.029 1.00 54.97 A ATOM 24 CA ILE A 4 -3.305 30.085 110.805 1.00 52.38 A ATOM 25 CB ILE A 4 -1.919 29.431 110.972 1.00 50.47 A ATOM 26 CG2 ILE A 4 -0.817 30.425 110.621 1.00 51.29 A ATOM 27 CG1 ILE A 4 -1.739 28.968 112.413 1.00 50.93 A ATOM 28 CD1 ILE A 4 -0.359 28.460 112.705 1.00 52.20 A x y z oc cu pa nc y b- fa ct or re sn am e ch ai n re si d na m e Pymol keywords se gi d Closeup of a pdb file Difference Distance Matrix • Compute distance matrix for each structure • Calculate the difference between each matix • Plot the differences This method highlights structural differences between two structures, and it doesn’t require superposition of the structures. linux download: http://roselab.jhu.edu/ddmp/ Comparison of open and closed forms of Yeast Coproporphyrinogen Oxidase -1.5Å to +1.5Å change in CA positions in the following regions: 81 to 107 134 to 147 265 to 283 Protein Alignments Sequence alignment compares amino-acid sequence Structural alignment compares 3-dimensional structure ? Structural alignment – how to… align - sequence alignment followed by structural superposition fit - structural superposition only rms - reports the rmsd from superposition rms_cur- reports the rmsd without superposition pair_fit - performs fit of defined atom pairs Pymol keywords: Output from an alignment includes: • Superposition of atomic coordinates (a pdb file) • RMSD (reports the divergence in the aligned structures) Polymerase Movie lsqman – generates intermediate frames (linux program) open closed Mg2+ 3’OH Pre-insertion site 5’ Open conformation Other comparison tools... Comparison Tools [top] 1. Structural Comparisons 1. Dali - Structural Comparison Server 2. Theseus - Maximum Liklihood alignment (run locally) Manual 3. DEJAVU - Uppsalla Software Factor Structural Comparison Server - based on secondary structural elements 4. VAST - (NCBI) Vector Alignment of Search Tool - protein structural neighbors 5. MSDServer - Macromolecular Structure Database (Can provide similarity cutoff to see entire structural family) to . Structural / Sequence Alignments 1. SSM - Secondary Structure Matching - multiple PDB comparison and sequence alignments. STAMP - Structural Alignment of Multiple Proteins to “ Indonesia - USF's biological sequence analysis (not installed) MUSTANG - A MUtiple STructure AligNment alGorithm (installed) PDF . SCOP - Structural Classification of Proteins . CATH - Structural Classification . PISA-Protein Interfaces, Surfaces and Assemblies (using PDB or new coordinates) we * . ElNemo Elastic Network Model (conformational changes) . EDS-Electron Density Server - Check other people's data cod At fk . SPIN - Surface Properties of [Nterfaces - Protein-Protein Interactions (see htt ps://wasat ch.biochem.ut ah.edu/ chris/ links/ links.ht ml)