Here, in collaboration with experimentalists, we computationally model: 1) fibrils assembled from single amino acid tryptophan; 2) inhibition of growth of tyrosine, phenylalanine, and adenine fibrils with the inhibitors tannic acid (TA) and epigallocatechin gallate (EGCG); 3) interactions of adenine, tryptophan, and tyrosine fibrils with 100% PC and 90%-10% PC-PS combination lipid bilayers. First, in molecular dynamics (MD) simulations, we examined structures of tryptophan fibrils and the potential way in which these fibrils could exhibit a stable unidirectional growth. Second, in agreement with experimental results, the simulations show that TA and EGCG prevent crystallization of metabolites, by binding to the solvated molecules of these metabolites. Both experiments and simulations show that TA inhibits metabolite assembly more effectively than EGCG, as TA-metabolite interactions are found to be stronger than EGCG-metabolite interactions. Finally, we simulate binding modes of metabolite fibrils with the lipid bilayers, to provide molecular description of the experimental results that fibrils contribute to necrosis via interactions with lipid membranes. Our simulations show that metabolite fibrils interact with both lipid bilayer types via a combination of electrostatic and dispersion interactions, though the former tends to be either equal or more dominant than latter.

Molecular dynamics simulations of metabolite fibrils

253rd National Meeting (2017)

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