Targeting Collagen Type III in Proteinuric Kidney Disease: Informing Drug Potential Using the Jaccard–Tanimoto Index

Abstract

Collagenofibrotic glomerulopathy, a collagen type III kidney disease, is associated with proteinuria and accumulation ofcollagen type III in the glomerulus specifically the mesangium and/or capillary walls. The puromcyin aminonucleoside (PAN) nephropathy model was evaluated to examine the relation between COL3A1 mRNA and proteinuria. In Wistar rats administered PAN, a robust increase in proteinuria was accompanied by glomerular hypertrophy and expansion of both the Bowman’s capsule and Bowman’s space. An ~4-fold increase in renal COL3A1 mRNA was observed in the PAN cohort with urine protein exhibiting a direct (r = 0.8) and significant correlation with kidney COL3A1 mRNA level. Both Picrosirius red polarized microscopy and immunohistochemical analysis showed localization of collagen type III to the glomerular mesangium. Gene ontology-driven transcriptomic analysis reveals a robust COL3A1 network in the glomerular compartment.

Recalibrating the calcium trap in amino acid carboxyl groups via classical molecular dynamics simulations

“…In the systems with biomolecules, two Na 2+ were added as background electrolytes to charge balance the 2e-overall charge of the biomolecule. We created four different starting configurations, to enhance the statistics of the results, and a similarity analysis between the initial configurations was conducted to quantify the differences in ion distributions using the Tanimoto distance [30][31][32] . For the Tanimoto distance, the vectors (configuration A and B, equation ( 1)) were ordered according to the distance to the center of mass (COM) of the biomolecule, whereas the pure systems were created by removing L-Asp from the starting configurations.…”

“…We created four different starting configurations, to enhance the statistics of the results, and a similarity analysis between the initial configurations was conducted to quantify the differences in ion distributions using the Tanimoto distance. [30][31][32] For the Tanimoto distance, the vectors (configuration A and B, eqn (1)) were ordered according to the distance to the center of mass (COM) of the biomolecule, whereas the pure systems were created by removing L-Asp from the starting configurations. The vectors contain, first, the distance between the atom closest to the COM of the biomolecule and the other atoms in the CaCO 3 cluster, followed by the distances between the atom closest to this first atom and the other atoms and so on.…”