Tensor Train Optimization for Conformational Sampling of Organic Molecules

ChemRxiv

Abstract

Exploring the conformational space of molecules remains a challenge of fundamental importance to quantum chemistry: identification of relevant conformers at ambient conditions enables predictive simulations of almost arbitrary properties. Here, we propose a novel approach to enable conformational sampling of large organic molecules where the combinatorial explosion of possible conformers prevents the use of a brute-force systematic conformer search. We employ tensor trains as a highly efficient dimensionality reduction algorithm, effectively reducing the scaling from exponential to polynomial. In our approach, the conformational search is expressed as global energy minimization task in a high-dimensional grid of dihedral angles. Dimensionality reduction is achieved through a tensor train representation of the high-dimensional torsion space. The performance of the approach is assessed on a variety of drug-like molecules in direct comparison to the state-of-the-art metadynamics based conformer rotamer ensemble sampling tool (CREST). The comparison shows significant acceleration of up to an order of magnitude, while maintaining comparable accuracy. More importantly, the presented approach allows treatment of larger molecules than typically accessible with metadynamics.

Authors 7

1. Christopher Zurek Aachen

   RWTH Aachen University

   Affiliation as printed

   RWTH Aachen University

2. Ruslan A. Mallaev

   Terra Quantum (Switzerland)

   Affiliation as printed

   Terra Quantum (Switzerland)

3. Alexander C. Paul

   Terra Quantum (Switzerland)

   Affiliation as printed

   Terra Quantum (Switzerland)

4. Nils van Staalduinen Aachen

   RWTH Aachen University

   Affiliation as printed

   RWTH Aachen University

5. Philipp Pracht

   Massachusetts Institute of Technology

   Affiliation as printed

   Massachusetts Institute of Technology

6. Roman Ellerbrock

   Terra Quantum (Switzerland)

   Affiliation as printed

   Terra Quantum (Switzerland)

7. Christoph Bannwarth Aachen

   RWTH Aachen University

   Affiliation as printed

   RWTH Aachen University