Parameterization of a sequence-specific coarse-grained collagen model.

Abstract

Collagen, excreted from cells as stiff, ∼1000-residue long trimers characterized by Gly-X-Y repeats, serves as the molecular skeleton of extracellular matrices (ECMs) through formation of fibrils and fibers. The mechanics and structure of collagen fibers and the ECM are currently modeled through “top-down” approaches, in which the structure and mechanics of the ECM are estimated from shape and average molecular composition. A "bottom-up" approach, employing both details at the molecular level and statistical data on collagen interactions in sequence and the PDB, may be used to develop coarse-grained (CG) molecular dynamics (MD) simulation models of collagen capable of representing fibril-level structures with sequence specificity. Using atomistic MD simulations rigorously validated on crystal structures, NMR, small-angle X-ray scattering experiments, atomic force microscopy, and optical tweezer experiments, we have developed internal parameters for a CG model of collagen. Sequence-specific interactions between collagens have been developed and tested using collagen sequence data and structures of collagen fibrils. We present the current state of our CG MD model and simulations of collagen fibrilization.