PolyChord is transforming the landscape of small-molecule analysis with Molytics, our cutting-edge technology that reveals the lowest energy state of molecules and small-molecule complexes. Unique to our full-coverage sampling of the energy function, is the provision of information about the vibrational modes of the molecules and complexes, and the ability to probe the molecular structure and vibrational modes at any temperature. By unlocking this level of molecular detail, we’re pioneering solutions that drive sustainable innovation across critical industries.
On the left we show a PolyChord sampling of the configuration space of the chemical we seek to replace with a more environmentally-friendly alternative, and a Copper catalyst. As the sampling advances it converges around the ground states for this complex, and provides information about its vibrational modes.
The PolyChord sampler is being used to map out the energy functions of small molecules (and their complexes). It is a state-of-the-art nested sampling algorithm [1], particularly adept at exploring complex parameter spaces with multiple local minima, where traditional sampling methods will falter.
We have developed our approach by leveraging the natural link between statistical mechanics, information theory, and Bayesian inference. Recent advances in density-functional theory codes (e.g. https://fhi-aims.org/) now allow us to compute the free energy of molecular configurations with high accuracy, akin to solving the Schrödinger equation. By efficiently exploring these free-energy landscapes, PolyChord learns the natural configurations and vibrational behaviour of small molecules "blind". Furthermore, these properties can be explored using PolyChord's sampling output at any temperature.
This methodology has proven successful in materials science [2, 3] and has been recently used to accurately determine the structure and partition functions of molecules like Butane-1,4-diol and various alkanes. We believe this approach holds significant promise for drug design, enabling the identification of optimal molecular structures directly from their free-energy profiles. In the same way, it can aid discovery of new “green” small-molecule catalysts, solvents and enzymes.
[1] Handley, W. J.; Hobson, M. P.; Lasenby, A. N. (2015) - PolyChord: Nested Sampling for Cosmology, Monthly Notices of the Royal Astronomical Society, Vol. 450, p. L61-L65
[2] Ashton et al. (2022) - Nested sampling for physical scientists, Nature Reviews Methods Primers, volume 2, Article number: 39
[3] Pártay, L. B.; Bartók, A.P; Csányi, G (2014) - Nested sampling for materials: The case of hard spheres, Physical Review E, 89, 022302