A molecular dynamics study of the interprotein interactions in collagenfibrils

Abstract

Molecular dynamics simulations of collagen are used to investigate at the atomistic level the nature of the interprotein interactions that are present within a collagen fibril, and which are responsible for the fibril's thermodynamic stability. Simulations both of a collagen fibril and of a fully solvated tropocollagen are compared in order to study the interactions that arise between the proteins upon the process of fibrillogenesis. The interactions studied include direct interprotein hydrogen bonds, water-mediated interprotein hydrogen bonds, and hydrophobic interactions. The simulations are used to quantify the number of interprotein interactions; to study which functional groups contribute most towards the interactions; and to investigate the spatial distribution of interprotein interactions throughout the fibril's D period. The processes of collagen fibrillogenesis and protein folding are then compared with each other, because these two physical processes share many similarities in concept, but the latter has been studied more widely. Molecular dynamics simulations of a bacteriophage T4 lysozyme protein, both in its native state and in an unfolded state, are used as an illustrative example of a typical protein folding process, for direct comparison with the collagen simulations.