Molecular evolution is a critical research focus in the
post-genome age of biology. With the current explosion of genome sequencing
projects and the expansion of biomolecular structure databases, we
finally have the opportunity to comprehensively appreciate and study
the diversity and diversification of biological molecules. My research
is focused on four areas within this field: 1) the origin and evolution
of the approximately 1000 known basic types of protein structure,
called folds; 2) the evolution of the function of sequence-specific
DNA-binding proteins; 3) the evolution of proteins to avoid incorrect
folding and aggregation, which can lead to many diseases, including
Alzheimer's and prion disorders; 4) the evolution of protein toxins
from nontoxic ancestor proteins. We approach these problems using
a combination of computational studies (bioinformatics) with experimental
structural biology (NMR and X-ray crystallography), biochemistry,
and protein design. Perhaps the best example of our research progress
to date is our characterization of a remarkable evolutionary structural
metamorphosis, involving a switch from alpha-helical to beta-sheet
secondary structure, in the Cro family of transcription factors (see
Van Dorn et al, 2006; Newlove et al, 2004).
Any link on the below references will take you off
of the BMCB site and to an abstract of that particular paper.
Patki, A.U., A.C. Hausrath, and M.H.J. Cordes. 2006. High polar content
of long buried blocks of sequence in protein domains suggests selection
against amyloidogenic nonpolar sequences. Journal of Molecular
Biology (in press).
Van Dorn, L.O., T. Newlove, S. Chang, W.M. Ingram, and M.H.J. Cordes.
2006. Relationship between sequence determinants of stability for
two natural homologous proteins with different folds. Biochemistry (in press).
Newlove, T., K.R. Atkinson, L.O. Van Dorn, and M.H.J. Cordes. 2006.
A trade between similar but nonequivalent intrasubunit and intersubunit
contacts in Cro dimer evolution. Biochemistry 45: 6379-6391.
Cordes, M.H.J., and G.J. Binford. 2006. Lateral gene transfer of
a dermonecrotic toxin between spiders and bacteria. Bioinformatics 22: 264-268.
Hall, B.M., K.R. LeFevre, and M.H.J. Cordes. 2005. Sequence correlations
between Cro recognition helices and cognate OR consensus half-sites
suggest conserved rules of protein-DNA recognition. Journal
of Molecular Biology 350: 667-681.
Binford, G.J., M.H.J. Cordes, and M.A. Wells. 2005. Sphingomyelinase
D from venoms of brown spiders: evolutionary insights from cDNA
sequences and gene structure. Toxicon 45: 547-560.
Newlove, T., J.H. Konieczka, and M.H. Cordes. 2004. Secondary structure switching in Cro protein evolution. Structure 12: 569-581.
