On the amino acid composition and mechanical stability of protein structures

Amino acid composition is an important determinant of protein structures. In this paper we investigate the relationship between amino acid composition and mechanical stability of protein sequences. We divide the protein structures deposited in the Protein Data Bank (PDB) as ordered, disordered and in the twilight zone, depending on their amino acid composition. We use a consensus score SSU among three predictors of global disorder, Poodle-W, gVSL2 and mean pairwise energy. Mechanical stability is evaluated through Miyazawa-Jernigan potential. We find that the three groups of protein sequences have different contact energy, disordered sequences being the most unstable and ordered ones being the most stable. Secondary structure energy and global mechanical stability, on the other hand, are about the same in the three groups of proteins, pointing to a fundamental role of backbone interactions in the stabilization of the tertiary structure. Proteins with relative high contact energy tend to remain short in length and they do not enrich in disorder-promoting amino acids. Moreover, several short proteins in the twilight zone compensate their relative instability through disulfide bridges. Our results support the hypothesis that backbone interactions play a fundamental role in the stabilization of protein structures. However, the role of long-range interactions and its relation with protein length must be further investigated. It is necessary to develop a more fundamental theory to understand the exact relation between amino acid composition and the mechanical stability of protein sequences.