Entropic control of the relative stability of triple-helical collagen peptide models.
Herein, we show that current methodologies in atomistic simulations can yield reliable standard free energy values in aqueous solution for the transition from the dissociated monomeric form to the triple-helix state of collagen model peptides. The calculations are performed on a prototypical highly stable triple-helical peptide, [(Pro-Hyp-Gly)10]3 (POG10), and on the so-called T3-785 triple-helix mimicking a fragment from the type III human collagen, which is more thermally labile. On the basis of extensive MD simulations in explicit solvent followed by molecular-mechanical and electrostatic Poisson-Boltzmann calculations complemented with an accurate estimation of the nonpolar contributions to solvation, the computed free energy change for the aggregation processes of the POG10 and T3-785 peptides leading to their triple-helices is -6.6 and -6.1 kcal/mol, respectively. For POG10, this value is in agreement with differential scanning calorimetric data. However, it is shown that conformational entropy, which is estimated by means of an expansion of mutual information functions, preferentially destabilizes the triple-helical state of T3-785 by around 4.6 kcal/mol, thus explaining its lower thermal stability. Altogether, our computational results allow us to ascertain, for the first time, the actual thermodynamic forces controlling the absolute and relative stability of collagen model peptides.
Suárez
Ernesto
E
Departamento de Química Física y Analítica, Universidad de Oviedo, Oviedo, Spain.
Díaz
Natalia
N
Suárez
Dimas
D
D002152:Calorimetry, Differential Scanning; D003094:Collagen / Q000737:chemistry*; D019277:Entropy; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry*
D010455:Peptides; D003094:Collagen