Structure and mechanism of maximum stability of isolated alpha-helical protein domains at a critical length scale

• Main Authors: Qin, Zhao (Contributor), Fabre, Andrea (Contributor), Buehler, Markus J (Contributor)
• Other Authors: Massachusetts Institute of Technology. Center for Materials Science and Engineering (Contributor), Massachusetts Institute of Technology. Center for Computational Engineering (Contributor), Massachusetts Institute of Technology. Department of Chemical Engineering (Contributor), Massachusetts Institute of Technology. Department of Civil and Environmental Engineering (Contributor), Massachusetts Institute of Technology. Laboratory for Atomistic and Molecular Mechanics (Contributor)
• Format: Article
• Language: English
• Published: Springer Berlin Heidelberg, 2016-10-06T22:29:44Z.
• Subjects: Article
• Online Access: Get fulltext

 The stability of alpha helices is important in protein folding, bioinspired materials design, and controls many biological properties under physiological and disease conditions. Here we show that a naturally favored alpha helix length of 9 to 17 amino acids exists at which the propensity towards the formation of this secondary structure is maximized. We use a combination of thermodynamical analysis, well-tempered metadynamics molecular simulation and statistical analyses of experimental alpha helix length distributions and find that the favored alpha helix length is caused by a competition between alpha helix folding, unfolding into a random coil and formation of higher-order tertiary structures. The theoretical result is suggested to be used to explain the statistical distribution of the length of alpha helices observed in natural protein structures. Our study provides mechanistic insight into fundamental controlling parameters in alpha helix structure formation and potentially other biopolymers or synthetic materials. The result advances our fundamental understanding of size effects in the stability of protein structures and may enable the design of de novo alpha-helical protein materials.