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Configurational entropy elucidates the role of salt‐bridge networks in protein thermostability
Author(s) -
Missimer John H.,
Steinmetz Michel O.,
Baron Riccardo,
Winkler Fritz K.,
Kammerer Richard A.,
Daura Xavier,
van Gunsteren Wilfred F.
Publication year - 2007
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1110/ps.062542907
Subject(s) - thermostability , salt bridge , molecular dynamics , accessible surface area , entropy (arrow of time) , root mean square , chemistry , chemical physics , thermal stability , protein engineering , protein folding , conformational entropy , thermal fluctuations , coiled coil , configuration entropy , thermodynamics , computational chemistry , physics , molecule , enzyme , biochemistry , organic chemistry , quantum mechanics , mutant , gene
Detailed knowledge of how networks of surface salt bridges contribute to protein thermal stability is essential not only to understand protein structure and function but also to design thermostable proteins for industrial applications. Experimental studies investigating thermodynamic stability through measurements of free energy associated with mutational alterations in proteins provide only macroscopic evidence regarding the structure of salt‐bridge networks and assessment of their contribution to protein stability. Using explicit‐solvent molecular dynamics simulations to provide insight on the atomic scale, we investigate here the structural stability, defined in terms of root‐mean‐square fluctuations, of a short polypeptide designed to fold into a stable trimeric coiled coil with a well‐packed hydrophobic core and an optimal number of intra‐ and interhelical surface salt bridges. We find that the increase of configurational entropy of the backbone and side‐chain atoms and decreased pair correlations of these with increased temperature are consistent with nearly constant atom‐positional root‐mean‐square fluctuations, increased salt‐bridge occupancies, and stronger electrostatic interactions in the coiled coil. Thus, our study of the coiled coil suggests a mechanism in which well‐designed salt‐bridge networks could accommodate stochastically the disorder of increased thermal motion to produce thermostability.