The role of water in host-guest interaction

DOI

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.

Identifier
DOI https://doi.org/10.24435/materialscloud:p3-1x
Related Identifier https://arxiv.org/abs/2006.13274
Related Identifier https://doi.org/10.1038/s41467-020-20310-0
Related Identifier https://archive.materialscloud.org/communities/mcarchive
Related Identifier https://doi.org/10.24435/materialscloud:44-xp
Metadata Access https://archive.materialscloud.org/oai2d?verb=GetRecord&metadataPrefix=oai_dc&identifier=oai:materialscloud.org:536
Provenance
Creator Rizzi, Valerio; Bonati, Luigi; Ansari, Narjes; Parrinello, Michele
Publisher Materials Cloud
Contributor Rizzi, Valerio; Bonati, Luigi; Ansari, Narjes; Parrinello, Michele
Publication Year 2020
Rights info:eu-repo/semantics/openAccess; Creative Commons Attribution 4.0 International; https://creativecommons.org/licenses/by/4.0/legalcode
OpenAccess true
Contact archive(at)materialscloud.org
Representation
Language English
Resource Type info:eu-repo/semantics/other
Format application/zip; text/plain; text/markdown
Discipline Materials Science and Engineering