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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
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JKS SEMINAR Oznur Tastan November 21, 2005 Property Based Conservation Percolation in Transmembrane Proteins
Percolation Threshold, pc Percolation theory deals with the connectivity of components a system. p<pc there is no infinite cluster p>pc there is one infinite cluster White balls => nonconducting spheres Black ball =>conducting spheres . Only above a certain concentration pc of the conducting balls the system conducts electrical current.
Membrane Folding Klein-Seetharaman,J., 2005
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 proteins 4. Initial program of percolation
PDBTM • PDB-TM is a new database for tm proteins with known structures (Tusnady et. al. 2004). * weekly updated http://pdbtm.enzim.hu/ Membrane approximation and oriented structures with respect to the menbrane Rhodopsin 1u19, A
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
Hydrophobic percentage All 6 hydrophobicity sets share the same six amino acids: Ile, Leu, Val, Phe, Trp, Met. As expected membrane proteins contains more hydrophobic residues on the average.
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 children Grow cluster until there is no neighbors Continue until there is no occupied cell Hydrophobic Clusters residues in Rhodopsin
Largest cluster of hydrophobic residues at 7 6 Å cutoff The largest cluster of hydrophobic residues at 6 Å cutoff.
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
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
Bacteriodopsin and Rhodopsin Green is bacteriorhodopsin Blue is rhodopsin
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
To be continued.. • Thanks to Naveena, Judith, Jaime and Hagai