Selective vitamins as potential options for dietary therapeutic interventions: In silico and In vitro insights from...

We have used an integrated computational approach to explore the role of vitamin C and vitamin D in preventing aggregation of Fibrinogen A alpha-chain (FGA^cter) protein responsible for renal amyloidosis. We modelled structures of E524K / E526K mutants of FGA^cter protein and examined the potential interactions of these mutants with vitamin C and vitamin D3. Interaction of these vitamins at the amyloidogenic site may prevent the intermolecular interaction required for amyloid formation. The binding free energy values of vitamin C and vitamin D3 for E524K FGA^cter and E526K FGA^cter are - 67.12 ± 30.46 kJ/mole and - 79.45 ± 26.12 kJ/mol, respectively. Experimental studies using Congo red absorption, aggregation index studies and AFM imaging show encouraging results. The AFM images of E526K FGA^cter contained more extensive and higher protofibril aggregates, whereas, in the presence of vitamin D3, small monomeric and oligomeric aggregates were observed. Overall, the works provide interesting results about vitamin C and D role in preventing renal amyloidosis.