# Measurement

> Ultra-fast hydrogen-deuterium exchange reads disordered proteins in solution and catches the transient structure that appears in milliseconds.

[View this page on Peptone](https://peptone.io/technology/hdx-ms/)

Reading a shape-shifting protein directly in solution, fast enough to catch structure that lasts only milliseconds.

## Overview

What if we could see structural states that no conventional experiment or frontier AI model can resolve?

- The most consequential states in a disordered protein are often the hardest to observe. They emerge at low population, open a binding pocket for only milliseconds, then disappear into the ensemble. Conventional experiments average over that motion, while AI models cannot recover states that the available evidence does not constrain.
- Ultra-fast hydrogen-deuterium exchange mass spectrometry turns that blind spot into a measurement. Exchange rates record which regions are exposed and which remain protected. By reading below 50 milliseconds, Peptone captures transient structural contrast before it washes out and converts it into residue-level constraints for ensemble modeling.

## At a glance

- Residue-level readout of protection and exposure across the full sequence
- Sub-fifty-millisecond time resolution from continuous-flow ultra-fast mixing
- Sensitivity to transient, low-population states that conventional HDX-MS cannot resolve
- Direct measurement in solution, with no crystal or fixed structure required
- Constraints that feed ensemble modeling rather than a single static model
- A shared evidence layer that keeps computation and experiment in one loop

## Headline

We can. For the first time.

Ultra-fast HDX-MS captures structural states that conventional experiments and frontier AI models cannot resolve, before their signal disappears.

Ultra-fast mixing opens the sub-50-millisecond window, before transient protection disappears.

## Speed Story

### Exposure

#### Headline

Read exchange from the first milliseconds.

Deuterium reaches the chain. Solvent-exposed backbone amides label first, while protected regions exchange more slowly.

Deuterium labels exposed amides first. Protected regions remain distinct only at the earliest time points.

### Selective

#### Headline

Preserve the contrast that reveals structure.

In the first milliseconds, local structure shields some amides while neighboring loops label. That difference is the structural signal.

Ultra-fast sampling separates protected sites from exposed loops before their uptake profiles converge.

### Washout

#### Headline

Classical time points erase that contrast.

At seconds-scale time points, deuterium has spread across the chain. Transient protection washes out and distinct regions look alike.

At seconds-scale reads, exchange has spread across the chain and transient structural differences are no longer distinguishable.

### Ultrafast

#### Headline

Measure up to 10,000× earlier.

Peptone measures below 10 milliseconds while position-specific protection still separates one conformation from another.

Peptone reads below 10 ms versus a 100 s measurement, while position-specific protection remains measurable.

### Pocket

#### Headline

Resolve pockets that exist for milliseconds.

The short-time protection pattern becomes a quantitative structural constraint for ensemble modeling.

A binding-competent conformation remains visible at 20 ms and becomes a quantitative constraint for ensemble modeling.

### Final Comparison

#### Headline

Earlier measurement preserves hidden states.

Earlier measurement preserves the contrast needed to resolve hidden states.

The exchange chemistry is unchanged. The advantage is reading it before structural contrast washes out.

#### Slow

##### Classical HDX-MS

##### Time

Seconds

Transient protection has washed out.

#### Fast

##### Ultra-fast HDX-MS

##### Time

Below 50 ms

Position-specific protection remains visible.

### Future System

#### Headline

The next frontier is in-cell measurement.

We are continuously evolving our HDX-MS capabilities and developing an integrated system designed to enable in-cell measurements of proteins in their biological context.

#### Origin Label

Proudly made in Switzerland