Molecular Dynamics Investigation on the Effects of Protonation and Lysyl Hydroxylation on Sulfilimine Cross-links in Collagen IV

Abstract

Collagen IV networks are an essential component of basement membranes that are important for their structural integrity and thus that of an organism's tissues. Improper functioning of these networks has been associated with several diseases. Cross-links, such as sulfilimine bonds interconnecting NC1 domains, are critical for forming and mechanically stabilizing these collagen IV networks. More specifically, the sulfilimine crosslinks form between methionine (Met93) and lysine/hydroxylsine (Lys211/Hyl211) residues of NC1 domains. Therefore, the dynamic nature of the sulfilimine bond in collagen IV is crucial for network formation. To understand the dynamic nature of a neutral and protonated sulfilimine bond in collagen IV, we performed molecular dynamics (MD) simulations on four sulfilimine cross-linked systems (i.e.

Sulfilimine bond formation in collagen IV

“…In 2022, we conducted molecular dynamics simulations on collagen IV containing neutral and protonated sulfilimine bonds to explore the dynamic stability of the bond and the effects of protonation. 74…”

“…In 2022, we conducted molecular dynamics simulations on collagen IV containing neutral and protonated sulfilimine bonds to explore the dynamic stability of the bond and the effects of protonation. 74 More specifically, four possible sulfilimine crosslinked collagen IV systems were considered: Met93 S-N Lys211 , Met93 S-NH Lys211 + , Met93 S-N Hyl211 , and Met93 S-NH Hyl211 + . In particular, 100 ns atomistic MD simulations were performed to study conformational motions of the sulfilimine bond in collagen IV in aqueous environments.…”

MOLECULAR DYNAMICS SIMULATIONS OF THE AFFINITY OF CHITIN AND CHITOSAN FOR COLLAGEN: THE EFFECT OF pH AND THE PRESENCE OF SODIUM AND CALCIUM CATIONS

“…After reaching the steepest gradient in the annealing simulations, MD calculations were performed with a different force field for each molecule in the considered systems: AMBER14 (collagen), GLYCAM06 (chitin/chitosan), and TIP3P (water). There was no threshold considered in the case of the Particle Mesh Ewald protocol [55], which was applied at the electrostatic contact detection step [56], while in the case of van der Waals forces, the 10-Å threshold was included (the default AMBER criterion). The standard parameters were utilised to integrate motion equations, namely multiple time steps of 1.25 and 2.5 fs for bonded interactions in the case of non-bonded forces and isothermal-isobaric conditions (temperature = 310 K, pressure = 1 atm) [53].…”

Collagen Type II—Chitosan Interactions as Dependent on Hydroxylation and Acetylation Inferred from Molecular Dynamics Simulations

“…Simulation box containing complexes of interest was filled with water and chloride ions to keep the system electrostatically neutral. Noteworthy, the AMBER14 force field applied for collagen shows good recreation of protein dynamics and ensures that the proper configurations and conformations of residues are maintained [64][65][66]. All calculations were carried out using the YASARA software [67].…”