Polish Infrastructurefor 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, T. JADCZYK, M. Malawski, M. Bubak, and I. Rotermanand I. Roterman

ACC Cyfronet AGHACC Cyfronet AGH

Cracow Grid WorkshopKrakow, 09.11.2011

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OutlineOutline

Protein folding process and Fuzzy Oil Drop (FOD) model FOD algorithm FOD experiment workflow Sequences and proteins' structures comparison

Tools usedConservation score

Searching for common structure motifs - experiment workflow

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Fuzzy Oil Drop modelFuzzy 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

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Fuzzy Oil Drop – algorithm structureFuzzy 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

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Fuzzy Oil Drop – algorithm structureFuzzy Oil Drop – algorithm structure

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Fuzzy Oil Drop – experiment workflowFuzzy Oil Drop – experiment workflow

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Fuzzy Oil Drop – GS2 Experiment WorkbenchFuzzy Oil Drop – GS2 Experiment Workbench

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Fuzzy Oil Drop – experiment resultsFuzzy Oil Drop – experiment results

Input: PDB Database (March 2011), 71100 files, 11.4GB Final Results: 68100 proteins, 321800 chains

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Structure and Sequence comparisonStructure 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

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Structure and sequence comparison - experimentStructure and sequence comparison - experiment

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Thanks for your attention!