Eur. Phys. J. E (2013) 36: 53
https://doi.org/10.1140/epje/i2013-13053-8

Regular Article

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

¹⁹⁸⁶⁷ Laboratory for Atomistic and Molecular Mechanics (LAMM), Department of Civil and Environmental Engineering, Massachusetts Institute of Technology, 77 Massachusetts Ave., 02139, Cambridge, MA, USA
²⁹⁸⁶⁷ Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Ave., 02139, Cambridge, MA, USA
³⁹⁸⁶⁷ Center for Computational Engineering, Massachusetts Institute of Technology, 77 Massachusetts Ave., 02139, Cambridge, MA, USA
⁴⁹⁸⁶⁷ Center for Materials Science and Engineering, Massachusetts Institute of Technology, 77 Massachusetts Ave., 02139, Cambridge, MA, USA

^* e-mail: mbuehler@MIT.EDU

Received: 29 April 2012
Accepted: 5 April 2013
Published online: 29 May 2013

Abstract

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.