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Structural determinants of protein evolution

Research Achievements

Structural determinants of protein evolution

IGERT Trainee Eric Franzosa in Franzosa, E.A., Xia, Y. (2009). Structural determinants of protein evolution are context-sensitive at the residue level. Molecular Biology and Evolution: 26, 2387-2395. Using homology-mapped yeast protein structures, we explore the relationships between residue evolution and continuous structural properties of the residue microenvironment. We confirm the role of solvent exposure as a major structural determinant of residue evolution and identify a weak secondary effect arising from packing density. We find that increasing protein-core size yields a rapid relaxation of selective constraint as solvent exposure increases, although solvent-excluded residues remain similarly constrained. Finally, we analyze selective constraint in protein-protein interfaces and detect two separable components: a continuous structural constraint that scales with total residue burial and a fixed functional constraint that accompanies any degree of interface involvement.