# Water Accelerates in the Hydration Shell of the N- and C‑Terminal Domains of α‑Synuclein in the Presence of NaCl

## TL;DR

This study explores how salt affects water movement around parts of the α-synuclein protein, which is linked to Parkinson's disease.

## Contribution

The novel finding is that salt accelerates water movement in specific regions of α-synuclein, contradicting previous assumptions.

## Key findings

- Water in the hydration shell of the N- and C-terminal domains of α-synuclein accelerates with increased NaCl concentration.
- Faster water diffusion in these domains aligns with experimental truncation results.
- Salt-induced dehydration of these domains may influence α-synuclein aggregation.

## Abstract

α-Synuclein
(α-Syn) is an intrinsically disordered
protein (IDP) whose aggregation into fibrils is implicated in Parkinson’s
disease (PD). While benign α-Syn aggregation frequently occurs,
off-target aggregates are implicated in disease progression. Although
most mechanisms of toxic α-Syn aggregate formation are unknown,
high concentrations of salt ions have been shown to systematically
result in faster aggregation. Previous work suggests that salt slows
water in the hydration shell of α-Syn, promoting intermolecular
interactions. Here, we use polarizable molecular dynamics (MD) to
investigate the interactions between α-Syn and water in response
to an increased NaCl concentration. While we also find that the water
in the hydration shell of the nonamyloid-β component (NAC) domain
slows down with increasing salt concentration, the water in the hydration
shell of the N- and C-terminal domains accelerates. The segments of
the N- and C-terminal domains that show faster water diffusion kinetics
corroborate with truncation experiment results. Overall, our work
suggests that α-Syn aggregation is related to partial salt-induced
dehydration of the N- and C-terminal domains.