Structural determinant of protein designability.
Here we present an approximate analytical theory for the relationship between a protein structure's contact matrix and the shape of its energy spectrum in amino acid sequence space. We demonstrate a dependence of the number of sequences of low energy in a structure on the eigenvalues of the structure's contact matrix, and then use a Monte Carlo simulation to test the applicability of this analytical result to cubic lattice proteins. We find that the lattice structures with the most low-energy sequences are the same as those predicted by the theory. We argue that, given sufficiently strict requirements for foldability, these structures are the most designable, and we propose a simple means to test whether the results in this paper hold true for real proteins.
England
Jeremy L
JL
Harvard University, Department of Chemistry and Chemical Biology, 12 Oxford Street, Cambridge, Massachusetts 02138, USA.
Shakhnovich
Eugene I
EI
D000596:Amino Acids / Q000737:chemistry; D008956:Models, Chemical; D009010:Monte Carlo Method; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013816:Thermodynamics
D000596:Amino Acids; D011506:Proteins