Effect of intrinsic and extrinsic factors on the simulated D-band length of type I collagen

Abstract

A signature feature of collagen is its axial periodicity visible in TEM as alternating dark and light bands. In mature, type I collagen, this repeating unit, D, is 67 nm long. This periodicity reflects an underlying packing of constituent triple-helix polypeptide monomers wherein the dark bands represent gaps between axially adjacent monomers. This organization is visible distinctly in the microfibrillar model of collagen obtained from fiber diffraction. However, to date, no atomistic simulations of this diffraction model under zero-stress conditions have reported a preservation of this structural feature. Such a demonstration is important as it provides the baseline to infer response functions of physiological stimuli. In contrast, simulations predict a considerable shrinkage of the D-band (11-19%). Here we evaluate systemically the effect of several factors on D-band shrinkage. Using force fields employed in previous studies we find that irrespective of the temperature/pressure coupling algorithms, assumed salt concentration or hydration level, and whether or not the monomers are cross-linked, the D-band shrinks considerably. This shrinkage is associated with the bending and widening of individual monomers, but employing a force field whose backbone dihedral energy landscape matches more closely with our computed CCSD(T) values produces a small D-band shrinkage of < 3%. Since this force field also performs better against other experimental data, it appears that the large shrinkage observed in earlier simulations is a force-field artifact. The residual shrinkage could be due to the absence of certain atomic-level details, such as glycosylation sites, for which we do not yet have suitable data.

X-Ray Diffraction Detects D-Periodic Location of Native Collagen Crosslinks In Situ and Those Resulting from Non- Enzymatic Glycation

“…Therefore, there are additional parameters required for molecular dynamic simulations to resemble the observed natural structure. Some of this can be attributed to the formation of AGEs as a result of normal physiological aging and/or sugar-mediated crosslinking [42]. The data presented here, give us insight into the location of these crosslinks including which amino acid residues are involved and can be used to refine the packing structure and associated simulations of type I collagen.…”

Environmentally controlled curvature of single collagen proteins

“…Many of the simulations of collagen have used steered molecular dynamics, which may not investigate its equilibrium flexibility. Additionally, the results of molecular dynamics simulations depend on the force fields used (41), which have been developed predominantly for globular proteins rather than the unique fold of collagen.…”

Nanomechanics of Type I Collagen

“…The N-and C-termini of all three peptides in a triple helix are capped individually, and the peptides are described using the all-atom Amber99sb-ildn force field (28,(32)(33)(34). The triple helix is placed in a cubic box containing explicit water molecules (~136 K), and water is described using SPC/E parameters (35).…”

“…The details of our MD simulation protocol are provided elsewhere (28), and here we provide only the salient points. Because the resolution of the crystal structure (PDB: 3HR2) was insufficient to reveal atomic level details, including side chain orientations and interpeptide hydrogen bonds (12,13), an atomically detailed model was constructed by incorporating the high-resolution crystallographic data of collagen-related peptides (12,28,41). The model includes all known hydroxylated forms of prolines and lysines, but not any glycosyl groups, as their specific sites remain unknown.…”

“…This serves as a control and also assesses the performance of MD against experiment. This is particularly important because we have demonstrated that the structural organization of triple helices in the fiber diffraction unit cell is sensitive to the employed MD protocol (28), and the question remains as to how well our protocol predicts the mechanics of isolated triple helices. We then determine the Young's modulus of the buried core of a fibril.…”