Halma Matthew T J, Tuszynski Jack A, Wuite Gijs J L
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.
Department of Physics, University of Alberta, 116 St 85 Ave, Edmonton, Alberta T6G 2R3, Canada.
Drug Discov Today. 2023 Jan;28(1):103443. doi: 10.1016/j.drudis.2022.103443. Epub 2022 Nov 14.
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.
生产新型治疗药物所需的时间和成本构成了巨大负担——典型的基于靶点的药物发现过程涉及药物库的计算筛选、化合物测定以及昂贵的临床试验。本综述总结了通过光镊获得的动态构象信息的价值,以及该信息如何针对“不可成药”的蛋白质。光镊提供了对生物机制与结构构象之间联系的深入理解,可用于药物发现。开发包括软件和样品制备在内的工作流程将提高通量,使光镊能够在生物制药领域得到应用。作为一种补充工具,光镊增加了候选药物的数量,增进了对靶点复杂结构动力学的理解,并阐明了化合物与其靶点之间的相互作用。