Detecting protein dissimilarities in multiple alignments using Bayesian variable selection.
BACKGROUND
We present an application of Bayesian variable selection to the novel detection of sequence elements that confer negative design to protein structure and function. As an illustration, we analyze the different dimer interfaces between the CXCL8 chemokine family with the CCL4 and CCL2 chemokine families to discover the changes that disfavor CXCL8 of quaternary structure.


RESULTS
In comparison with known experimental results, our method identifies evolutionarily conserved sequence changes in the CC families that inhibit CXCL8 quaternary structure. Therefore, we find positive selection of negative design elements. Furthermore, our approach predicts that a two-residue deletion conserved in the CCL4 chemokine family disfavors CXCL8 dimerization.


BACKGROUND
The Matlab code for the Bayesian variable selection is freely available at http://stat.tamu.edu/~mvannucci/webpages/codes.html
Kim
Sinae
S
Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA.
Tsai
Jerry
J
Kagiampakis
Ioannis
I
LiWang
Patricia
P
Vannucci
Marina
M
D000465:Algorithms; D000595:Amino Acid Sequence; D001499:Bayes Theorem; D017124:Conserved Sequence; D008969:Molecular Sequence Data; D010363:Pattern Recognition, Automated / Q000379:methods; D011506:Proteins / Q000737:chemistry*; D016415:Sequence Alignment / Q000379:methods*; D020539:Sequence Analysis, Protein / Q000379:methods*; D017386:Sequence Homology, Amino Acid; D012984:Software
D011506:Proteins