jks seminar oznur tastan november 21, 2005

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JKS SEMINAR Oznur Tastan November 21, 2005. Property Based Conservation Percolation in Transmembrane Proteins. PERCOLATION. Percolation Threshold, p c. Percolation theory deals with the connectivity of components a system. p< p c there is no infinite cluster - PowerPoint PPT Presentation

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JKS SEMINAR Oznur Tastan November 21, 2005

Property Based ConservationPercolation in Transmembrane Proteins

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PERCOLATION

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Percolation Threshold, pc

p< pc there is no infinite cluster

p> pc there is one infinite cluster

White balls => nonconducting spheresBlack ball =>conducting spheres .

Only above a certain concentration pc of the conducting balls the system conducts electrical current.

Percolation theory deals with the connectivity of components a system.

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Membrane Folding

Klein-Seetharaman,J., 2005

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So far…

Three very initial points have been explored:1. Membrane assignment of residues.2. Build a data set of up-to-date membrane proteins of structure known.3. The calculation of hydrophobic percentage of membrane proteins4. Initial program of percolation

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PDBTM

PDB-TM is a new database for tm proteins with known structures (Tusnady et. al. 2004).

* weekly updatedhttp://pdbtm.enzim.hu/

Membrane approximation and oriented structures with respect to the menbrane

Rhodopsin 1u19, A

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Membrane proteins compiled

There are 179 chains in the non-redundant alpha list of PDB-TM

Followings are excluded: structures with less than three

transmembrane helices. structures unusual very open

theoretical models

54 membrane protein chains

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Hydrophobic percentage

All 6 hydrophobicity sets share

the same six amino acids: Ile, Leu, Val, Phe, Trp, Met.

The three differing amino acids for each set:

Set 1 [Cys,His,Tyr]

Set 2 [Cys,Pro,Tyr]

Set 3 [Cys,Ala,Tyr]

Set 4 [Pro,Ala,Tyr]

Set 5 [Cys,Ala,Gly]

Set 6 [Pro,Ala,Gly]

Set 1 Set 2 Set 3 Set 4 Set 5 Set 6

Membrane <fprot>54 0.47 0.50 0.55 0.58 0.60 0.64

Soluble <fprot>103 0.35 0.37 0.42 0.44 0.47 0.49

As expected membrane proteins contains more hydrophobic residues on the average.

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Finding clusters, a breadth first search

Start from an occupied cell.Add the first neighbors of the origin to

the cluster, Add the first neighbors of childrenGrow cluster until there is no neighbors

Continue until there is no occupied cell

Hydrophobic Clusters residues in Rhodopsin Connectivity cutoff(Å) Number of clusters Size of largest cluster End-to-end distance of the largest cluster(Å)

7 6 161 61.55

6 16 104 55.76

5 65 12 15.12

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Largest cluster of hydrophobic residues at 7 6 Å cutoff

The largest cluster of hydrophobic residues at 6 Å cutoff.

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Property Based Conservation

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Rhodopsin and MGluR6 PBC comparison

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23 Properties selected

4 A contact number/Nishikawa-Ooi 8 A contact number/Nishikawa-Ooi Average accessible surface area/Janin Flexibility param for no rigid neighbors/Karplus-Schulz Flexibility param for one rigid neighbor/Karplus-Schulz Flexibility param for two rigid neighbors/Karplus Schulz7Hphob/Miyazawa/Roseman8 Hydropathy index/Kyte-Doolittle Long range non-bonded energy per atom/Oobatake-Ooi Normalized flexibility/B-values, average/Vihinen Normalized frequency of alpha-helix/Chou-Fasman Normalized frequency of beta-sheet/Chou-Fasman Normalized frequency of coil/Nagano Normalized frequency of turn/Crawford Normalized van der Waals volume/Fauchere Number of hydrogen bond donors/Fauchere Percentage of buried residues/Janin Polarity/Grantham Short and medium range non-bonded energy per residue/Oobatake-Ooi Side chain torsion angle phi/AAAR Levitt Volume/Grantham White Wimley Octanol Interface Scale Helix-PackingScale

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Method

The permutation test is not employed. Instead the results are normalized with background

probabilities, which are calculated class specific, by taking the frequencies of amino acid in each of the alignments

Positions that exhibit similar properties are identified. normalized conservation ratio, r normalized conservation difference, d consider similar behavior if|r-1| <0.05 or |d|

<0.01

37 positions to be examined in the folding core

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Rho116 Phe Mglur6-650 Leu

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Rho116 Phe MGluR6-650 Leu

'Average accessible surface area/Janin' 0.075881 0.09896'Percentage of buried residues/Janin' 0.18762 0.25537'Hphob/Miyazawa/Roseman' 0.2938 0.32786'Flexibility param for two rigid neighbors/Karplus-Schulz'0.33739 0.42779'8 A contact number/Nishikawa-Ooi' 0.39612 0.38902

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Bacteriodopsin and Rhodopsin

Green is bacteriorhodopsin

Blue is rhodopsin

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Rho116 Phe BacRho-85 Asp

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Rho116 Phe BacRho-85 Asp

'Average accessible surface area/Janin' 0.075881 0.15427

'Number of hydrogen bond donors/Fauchere' 0.084191 0.14124

'Percentage of buried residues/Janin' 0.18762 0.16367

'Hydropathy index/Kyte-Doolittle' 0.23445 0.18368

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T4 lyzosome mutations

To be used in the PBC analysis. T4 lyzosome mutations are started to be

compiled The full mutation list is obtained from

ProTherm. There are 1068 entries. We collected all the available online papers

that is related to the mutations. Summarizing the effect and the nature of the

mutations

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To be continued..

Thanks to Naveena, Judith, Jaime and Hagai

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