Published September 28, 2020 | Version v1
Dataset Open

The role of water in host-guest interaction

  • 1. Department of Chemistry and Applied Biosciences, ETH Zurich, 8092 Zurich, Switzerland
  • 2. Facoltà di Informatica, Istituto di Scienze Computazionali, Università della Svizzera Italiana, Via G. Buffi 13, 6900 Lugano, Switzerland
  • 3. Department of Physics, ETH Zurich, 8092 Zurich, Switzerland
  • 4. Italian Institute of Technology, Via Morego 30, 16163 Genova, Italy

* Contact person

Description

One of the main applications of atomistic computer simulations is the calculation of ligand binding free energies. The accuracy of these calculations depends on the force field quality and on the thoroughness of configuration sampling. Sampling is an obstacle in simulations due to the frequent appearance of kinetic bottlenecks in the free energy landscape. Very often this difficulty is circumvented by enhanced sampling techniques. Typically, these techniques depend on the introduction of appropriate collective variables that are meant to capture the system's degrees of freedom. In ligand binding, water has long been known to play a key role, but its complex behaviour has proven difficult to fully capture. In this paper we combine machine learning with physical intuition to build a non-local and highly efficient water-describing collective variable. We use it to study a set of of host-guest systems from the SAMPL5 challenge. We obtain highly accurate binding free energies and good agreement with experiments. The role of water during the binding process is then analysed in some detail.

Files

File preview

files_description.md

All files

Files (3.3 GiB)

Name Size
md5:3e8f96704822560b8d4edde4129fa113
339 Bytes Preview Download
md5:16de2c2cd867afff3bbb7e4e54063851
3.3 GiB Preview Download
md5:cb78637dfc2a1a7e33f5bd45e9fe3d70
1.5 KiB Preview Download

References

Preprint
V. Rizzi, L. Bonati, N. Ansari, M. Parrinello, arXiv:2006.13274 (2020)

Journal reference
V. Rizzi, L. Bonati, N. Ansari, M. Parrinello, Nat. Commun. 12, 93 (2021), doi: 10.1038/s41467-020-20310-0