Effects of End-Terminal Capping on Transthyretin (105–115)‎ Amyloid Protofibrils Using Steered Molecular Dynamics

Abstract EN

Numerous degenerative diseases are associated with amyloidosis, which can be caused by amyloid proteins.

These amyloid proteins are generated from misfolded and denatured amyloid monomers under physiological conditions.

Changes in protonation state, pH, ionic strength, and temperature, in addition to mutations, are related to the promotion of amyloidosis.

Specifically, an understanding of the mechanical characteristics of amyloid protofibrils is important, since amyloid growth proceeds by a mechanism involving cycles of fragmentation and elongation.

However, there remains a lack of knowledge of amyloid structural conformations and their mechanical characteristics, particularly considering end-terminal capping effects.

In the present study, we investigated the mechanical characteristics of transthyretin amyloid protein (TTR), which have been implicated in cardiovascular disease, and specifically considered the contribution of end-terminal capping effects.

Using steered molecular dynamics (SMD) simulations, we report different structural behaviors between uncapped and capped TTR amyloid protofibrils.

We show that end-terminal capping strengthens the structural stability and improves the mechanical properties of amyloid protofibrils.

This study provides useful information concerning the structural and mechanical characteristics of TTR amyloid protofibrils, with a particular emphasis on end-terminal capping effects.