Protein Functional Site Prediction The identification of protein regions responsible for stability...
20
Protein Functional Site Prediction • The identification of protein regions responsible for stability and function is an especially important post-genomic problem • With the explosion of genomic data from recent sequencing efforts, protein functional site prediction from only sequence is an increasingly important bioinformatic endeavor.
-
date post
19-Dec-2015 -
Category
Documents
-
view
216 -
download
0
Transcript of Protein Functional Site Prediction The identification of protein regions responsible for stability...
Protein Functional Site Prediction
• The identification of protein regions responsible for stability and function is an especially important post-genomic problem
• With the explosion of genomic data from recent sequencing efforts, protein functional site prediction from only sequence is an increasingly important bioinformatic endeavor.
What is a “Functional Site”?
• Defining what constitutes a “functional site” is not trivial
• Residues that include and cluster around known functionality are clear candidates for functional sites
• We define a functional site as catalytic residues, binding sites, and regions that clustering around them.
Protein
Protein + Ligand
Functional Sites (FS)
Regions that Cluster Around FS
Phylogenetic motifs
• PMs are short sequence fragments that conserve the overall familial phylogeny
• Are they functional?
• How do we detect them?
Phylogenetic motifs
• PMs are short sequence fragments that conserve the overall familial phylogeny
• Are they functional?• How do we detect them? • First we design a simple heuristic to find
them• Then we see if the detected sites are
functional
Phylogenetic Motif Identification
• Compare all windowed trees with whole tree and keep track of the partition metric scores
• Normalize all partition metric scores by calculating z-scores
• Call these normalized scores Phylogenetic Similarity Z-scores (PSZ)
• Set a PSZ threshold for identifying windows that represent phylogenetic motifs
Set PSZ Threshold
Regions of PMs
TIM
Phylogenetic Similarity False Positive Expectation
TIM
Phylogenetic Similarity False Positive Expectation
Cytochrome P450
Phylogenetic Similarity False Positive Expectation
Cytochrome P450
Phylogenetic Similarity False Positive Expectation
Enolase
Phylogenetic Similarity False Positive Expectation
Glycerol Kinase
Phylogenetic Similarity False Positive Expectation
Glycerol Kinase
Phylogenetic Similarity False Positive Expectation
Myoglobin
Phylogenetic Similarity False Positive Expectation
Myoglobin
Phylogenetic Similarity False Positive Expectation
