Optical tweezers for drug discovery

Matthew T J Halma; Jack A Tuszynski; Gijs J L Wuite

doi:10.1016/j.drudis.2022.103443

Optical tweezers for drug discovery

Drug Discov Today. 2023 Jan;28(1):103443. doi: 10.1016/j.drudis.2022.103443. Epub 2022 Nov 14.

Authors

Matthew T J Halma¹, Jack A Tuszynski², Gijs J L Wuite³

Affiliations

¹ Department of Physics and Astronomy, Vrije Universiteit Amsterdam, De Boelelaan 1081, 1081 HV Amsterdam, The Netherlands; LUMICKS B.V, Paalbergweg 3, 1105 AG Amsterdam, The Netherlands.
² Department of Physics, University of Alberta, 116 St 85 Ave, Edmonton, Alberta T6G 2R3, Canada.
³ Department of Physics and Astronomy, Vrije Universiteit Amsterdam, De Boelelaan 1081, 1081 HV Amsterdam, The Netherlands. Electronic address: g.j.l.wuite@vu.nl.

PMID: 36396117
DOI: 10.1016/j.drudis.2022.103443

Abstract

The time taken and the cost of producing novel therapeutic drugs presents a significant burden - a typical target-based drug discovery process involves computational screening of drug libraries, compound assays and expensive clinical trials. This review summarises the value of dynamic conformational information obtained by optical tweezers and how this information can target 'undruggable' proteins. Optical tweezers provide insights into the link between biological mechanisms and structural conformations, which can be used in drug discovery. Developing workflows including software and sample preparation will improve throughput, enabling adoption of optical tweezers in biopharma. As a complementary tool, optical tweezers increase the number of drug candidates, improve the understanding of a target's complex structural dynamics and elucidate interactions between compounds and their targets.

Keywords: biological mechanism; conformation; drug discovery; optical tweezers; target identification; undruggable proteins.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Drug Discovery
Molecular Conformation
Optical Tweezers*
Proteins* / metabolism

Substances

Proteins