Tensor Train Optimization for Conformational Sampling of Organic Molecules

Journal of Chemical Theory and Computation, vol. 21, pp. 1459–1475

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, called TTConf, 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 search as implemented in 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 Institute of Physical Chemistry

   RWTH Aachen University

   Affiliation as printed

   Institute of Physical Chemistry

   RWTH Aachen University

   Institute of Physical Chemistry, RWTH Aachen University, Aachen 52074, Germany

2. Ruslan A. Mallaev

   Terra Quantum (Switzerland)

   Affiliation as printed

   Terra Quantum AG

   Terra Quantum AG, St. Gallen 9000, Switzerland

3. Alexander C. Paul

   Terra Quantum (Switzerland)

   Affiliation as printed

   Terra Quantum AG

   Terra Quantum AG, St. Gallen 9000, Switzerland

4. Nils van Staalduinen Aachen Institute of Physical Chemistry

   RWTH Aachen University

   Affiliation as printed

   Institute of Physical Chemistry

   RWTH Aachen University

   Institute of Physical Chemistry, RWTH Aachen University, Aachen 52074, Germany

5. Philipp Pracht

   Massachusetts Institute of Technology

   Affiliation as printed

   Department of Chemical Engineering

   Massachusetts Institute of Technology

   Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States

6. Roman Ellerbrock corresponding

   Terra Quantum (Switzerland)

   Affiliation as printed

   Terra Quantum AG

   Terra Quantum AG, St. Gallen 9000, Switzerland

7. Christoph Bannwarth corresponding Aachen Institute of Physical Chemistry

   RWTH Aachen University

   Affiliation as printed

   Institute of Physical Chemistry

   RWTH Aachen University

   Institute of Physical Chemistry, RWTH Aachen University, Aachen 52074, Germany