# Modeling

> Experimentally constrained ensembles reveal the rare states and transient structure that static models cannot resolve.

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

Rebuilding the full range of shapes a protein moves through, so supported low-population states come into view.

## Overview

A disordered protein is a population, not a single structure.

- That population spans dominant disordered conformations and rare states that appear only briefly. No single structure can represent the target, and simulation alone cannot determine which states the protein actually occupies.
- Peptone combines HDX-MS measurements in solution with OPES enhanced sampling and physiological reweighting to recover the ensemble. NMR and EPR add orthogonal local and long-range restraints that test whether the modeled populations agree with experiment.

## At a glance

- Target-specific HDX-MS evidence integrated with ensemble generation
- OPES multithermal sampling reweighted to physiological conditions
- Oppenheimer and PepTron-o ensemble generation on accelerated infrastructure
- Ensemble populations weighted against HDX-MS, NMR, and EPR observables
- Rare-state populations resolved without collapsing the ensemble to one structure

## Computation follows the question.

- Enhanced sampling expands the conformational search; experimental agreement narrows it. Elastic AWS and NVIDIA infrastructure supplies the capacity required for simulation, reweighting, and inference while keeping each calculation tied to the measurements that determine what should be tested next.

### Video Title

Accelerated computing at Peptone

### Video Description

A short film on the infrastructure behind Peptone's ensemble-first, experimentally grounded Product Engine.

## References

- [A Disordered Protein Won't Hold Still for Its Portrait](https://idps.substack.com/p/a-disordered-protein-wont-hold-still)
- [Biotech's AI Revolution Will Be Won in the Lab](https://idps.substack.com/p/biotechs-ai-revolution-will-be-won)
- [Transient tertiary structure in intrinsically disordered proteins](https://www.nature.com/articles/s41467-026-73067-3)