Structural determinant of protein designability

• Published in: Physical review letters Vol. 90; no. 21; p. 218101
• Main Authors: England, Jeremy L, Shakhnovich, Eugene I
• Format: Journal Article
• Language: English
• Published: United States 30-05-2003
• Subjects: Amino Acids - chemistry; Models, Chemical; Monte Carlo Method; Protein Conformation; Proteins - chemistry; Structure-Activity Relationship; Thermodynamics
• ISSN: 0031-9007; 1079-7114
• DOI: 10.1103/PhysRevLett.90.218101

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.