# Self Consistent Path Sampling: Making Accurate All-Atom Protein Folding Simulations Possible on Small Computer Clusters

## TL;DR

This paper presents a novel iterative algorithm for accurate all-atom protein folding simulations that significantly reduces computational costs, enabling such simulations on small computer clusters.

## Contribution

The authors introduce a new path sampling algorithm based on the path integral formalism that efficiently computes protein folding pathways with realistic force fields.

## Key findings

- Validated on a fast folding protein, matching ultra-long MD simulations.
- Reduces computational cost from supercomputer to desktop level.
- Provides a stochastic estimate of the reaction coordinate.

## Abstract

We introduce a powerful iterative algorithm to compute protein folding pathways, with realistic all-atom force fields. Using the path integral formalism, we explicitly derive a modified Langevin equation which samples directly the ensemble of reactive pathways, exponentially reducing the cost of simulating thermally activated transitions. The algorithm also yields a rigorous stochastic estimate of the reaction coordinate. After illustrating this approach on a simple toy model, we successfully validate it against the results of ultra-long plain MD protein folding simulations for a fast folding protein (Fip35), which were performed on the Anton supercomputer. Using our algorithm, computing a folding trajectory for this protein requires only 1000 core hours, a computational load which could be even carried out on a desktop workstation.