# Science

> Learn how Peptone measures disordered proteins in motion, resolves transient pockets, and generates small-molecule drug candidates against them.

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Much of the human proteome never holds a fixed shape. Peptone reads, models, and drugs the biology in that motion

## Intrinsically disordered proteins

Most medicines are designed against proteins that hold a fixed shape. Much of what drives human disease never does. Roughly a third of residues in the human proteome never fold into a stable structure, and most human proteins carry at least one disordered region. These proteins do their job precisely because they stay in motion.

## A folded protein holds one shape. A disordered one does not

A folded protein settles into a single cooperative structure and presents a stable pocket. An intrinsically disordered protein moves continuously through a broad ensemble of interconverting conformations. For these proteins the ensemble is the molecule, and a single snapshot can be actively misleading.

## Disorder runs the control points of biology

Disordered regions concentrate at the busiest junctions of the cell, including transcription factors, signaling proteins, and membraneless condensates. Their failure contributes to stubborn diseases across oncology, CNS, immunology and inflammation, and longevity.

## Left out of the structural record

Structural biology was built around methods that need a static, cooperative subject. X-ray crystallography and cryo-electron microscopy resolve ordered structures beautifully and moving ensembles poorly, so much of the disordered proteome was set aside as undruggable.

## Frontier AI inherits the gap

Protein prediction models learned from the same archive of ordered structures. For a disordered target they can return a crisp static shape that the protein never actually holds, while their own residue-level confidence falls across the regions that matter most.

## We steer the physics with measurement

Peptone reads targets in solution and in motion using hydrogen-deuterium exchange mass spectrometry with magnetic and paramagnetic resonance spectroscopy. Sparse experimental restraints steer simulation and generative models toward thermodynamically sensible states that a protein truly populates.

## Proof: a rare state made visible

Multithermal enhanced sampling of ACTR resolved a binding-competent conformation populated about three percent of the time. The computed ensemble agreed with independent NMR and SAXS measurements, turning a pocket absent from average structures into a defined, addressable target.

## Every step serves one purpose

Peptone's Product Engine uses real biophysics to tighten each design, measure, and decide cycle and generate small-molecule drug candidates for rigorous preclinical and clinical evaluation against targets that structure-first discovery leaves untouched.