1. Polish Infrastructure for Supporting Computational Science in the European Research Space EUROPEAN UNION Examining Protein Folding Process Simulation and Searching for Common Structure Motifs in a Protein Family as Experiments in the GridSpace2 Virtual Laboratory T. JADCZYK, M. Malawski, M. Bubak, and I. Roterman ACC Cyfronet AGH Cracow Grid Workshop Krakow, 09.11.2011

2. 2 Outline Protein folding process and Fuzzy Oil Drop (FOD) model FOD algorithm FOD experiment workflow Sequences and proteins' structures comparison Tools used Conservation score Searching for common structure motifs - experiment workflow

3. 3 Fuzzy Oil Drop model  Protein Structure – chains, amino acids, atoms  Protein Folding – primary, secondary, tetriary structure  Fuzzy Oil Drop is Based on Kauzmann's Oil-Drop model of protein molecule  Assumes folding process directed by water environment  Extended from discrete one to 3-D Gauss function used to describe the idealized hydrophobicity distribution  Hydrophobic: "Water hating". Amino acids that prefer to be in a non-aqueous (lipid) environment because they cannot make favorable interactions with water.  The highest hydrophobicity concentration is expected in the center of the protein body, with the decrease of its values toward the surface, where the hydrophobicity is expected to be close to zero

4. 4 Fuzzy Oil Drop – algorithm structure  1. Input: PDB file  2. Simplify protein's residues to „effective atoms” representation  3. Find two furthest atoms, Move protein to origin center, rotate  4. Determine theoretical hydrophobicity distribution  5. Calculate observed hydrophobicity,  6. Test similarity of both distributions  7. Store results:  PDBID, chain, chain length, organism, method, function  O/T, O/R values  Future: O/T, O/R profiles

5. 5 Fuzzy Oil Drop – algorithm structure

6. 6 Fuzzy Oil Drop – experiment workflow

7. 7 Fuzzy Oil Drop – GS2 Experiment Workbench

8. 8 Fuzzy Oil Drop – experiment results  Input: PDB Database (March 2011), 71100 files, 11.4GB  Final Results: 68100 proteins, 321800 chains

9. 9 Structure and Sequence comparison  Search for conservative areas to discover protein function or find ligand binding site  Comparison on three levels of protein description:  Amino acid sequence  Structural codes  3D structures  W score to determine area's conservativeness  Used alignment tools:  ClustalW – multiple sequences alignment  Mammoth – multiple structures alignment

10. 10 Structure and sequence comparison - experiment

11. 11 Thanks for your attention!