Title: Computational Biology and Molecular Architecture Speaker: William R. Atchley, Department of Genetics, NCSU, Raleigh, NC Abstract Understanding the origin and evolution of gene expression patterns requires knowledge of the Òmolecular architectureÓ of DNA-transcription factor interactions, i.e., the relative composition of amino acids, their physiochemical properties, structure of the DNA-protein interaction, binding affinities among protein variants and a myriad of other features. Extensive laboratory analyses are conventionally used to ascertain molecular architecture. To short-circuit some of this, we are using multivariate statistical analyses on sequence data in transcriptional regulators to explore the molecular architecture of the DNA binding and dimerization regions. TodayÕs lecture deals with the application of multivariate discriminant analysis procedures to define subsets of amino acids whose simultaneous covariation accurately distinguishes the DNA binding groups in basic helix-loop-helix (bHLH) proteins. Further, important underlying physiochemical attributes important to these findings will be described. Part of the lecture with come from the following papers: Atchley, W. R. and J. Zhao. 2006. Molecular Architecture of the DNA Binding Region and its Relationship to Classification of Basic Helix-Loop-Helix Proteins. Molecular Biology and Evolution. In Press. [Pre-Print at http://www.atchleylab.org/] Atchley, W. R., J. Zhao, A. Fernandes and T. Drueke. 2005. Solving the sequence ÒmetricÓ problem: Proc. Natl. Acad. Sci. USA 102:6395-6400. [PDF reprint at http://www.atchleylab.org/]