Biology subjects

Coleman, L. M.

Publications and source records attributed to Coleman, L. M..

3 recordsLinked to original sources

bioRxiv2026

Modulating Transthyretin Fibril Stability with D-Retro-Inverso Peptides

A major cause of heart failure in elderly patients are deposits of Transthyretin (TTR) fibrils. Using molecular dynamic simulations, we explore how the stability of TTR fibrils can be modulated by D-Retro-Inverso (DRI) Peptides, built from D-amino acids with the sequence of the parent peptide switched, and describe a mechanism by which one of these peptides, DRI-K6V, disrupts TTR fibrils. Our results may open the way to design of peptide drugs targeting established TTR amyloidosis.

biophysics↗

bioRxiv2026

D-Retro-Inverso Peptide Candidates for Inhibiting SAA Cardiac Amyloidosis

In a recent study of a mice model it was suggested that after myocardial infarction Serum Amyloid A (SAA) aggregates are formed that contribute to the long-term complications of the infarct, and that a similar mechanism may exist for humans. Motivated by this hypothesis we have designed four peptide candidates that may interfere with formation of SAA3 fibrils, and using all-atom molecular dynamics have evaluated their ability to destabilize SAA fibrils. As the lifetime of peptide drugs can be increased by replacing L-amino acids with their mirror D-amino acids, we have built the peptides from D-amino acids. We identify two of these peptides, DRI-R5S and DRI-H6A, as promising drug candidates.

biochemistry↗

bioRxiv2025

The Effect of SARS-COV-2 Protein Fragments onthe Dimerization of α-Synuclein

There is evidence that amyloidogenic segments in SARS-COV-2 proteins can induce aggregation of -synuclein (S), the main component of brain-located amyloids whose presence is connected with Parkinsons Disease (PD). Using molecular dynamic simulations, we could show in earlier work that SARS-COV-2 protein fragments shift the ensemble of S chains toward more aggregation-prone conformations. However, the mechanism by which these chains assemble into fibrils, the presumed neurotoxic agent in PD, is not clear. The first step on that route are dimers. For this reason, we have now, using again molecular dynamics simulations, studied how the fragment 194FKNIDGYFKI203 (FI10) of the SARS-COV-2 spike protein, and the fragment 54SFYVYSRVK62 (SK9) of the envelope protein, alter the ensemble of -synuclein dimers. Our simulations suggest a differential stabilization of such dimers that would preferentially seed rod-like fibrils over the competing twister-like structures.

molecular biology↗