Center for Engineering in Medicine and BioMEMS Resource Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA; email:
Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA.
Annu Rev Biomed Eng. 2019 Jun 4;21:1-31. doi: 10.1146/annurev-bioeng-060418-052130. Epub 2018 Dec 10.
Successful stabilization and preservation of biological materials often utilize low temperatures and dehydration to arrest molecular motion. Cryoprotectants are routinely employed to help the biological entities survive the physicochemical and mechanical stresses induced by cold or dryness. Molecular interactions between biomolecules, cryoprotectants, and water fundamentally determine the outcomes of preservation. The optimization of assays using the empirical approach is often limited in structural and temporal resolution, whereas classical molecular dynamics simulations can provide a cost-effective glimpse into the atomic-level structure and interaction of individual molecules that dictate macroscopic behavior. Computational research on biomolecules, cryoprotectants, and water has provided invaluable insights into the development of new cryoprotectants and the optimization of preservation methods. We describe the rapidly evolving state of the art of molecular simulations of these complex systems, summarize the molecular-scale protective and stabilizing mechanisms, and discuss the challenges that motivate continued innovation in this field.
成功的生物材料稳定和保存通常利用低温和脱水来抑制分子运动。冷冻保护剂通常用于帮助生物实体在低温或干燥引起的理化和机械应力下存活。生物分子、冷冻保护剂和水之间的分子相互作用从根本上决定了保存的结果。使用经验方法优化的测定在结构和时间分辨率方面往往受到限制，而经典的分子动力学模拟可以以经济高效的方式洞察决定宏观行为的单个分子的原子级结构和相互作用。对生物分子、冷冻保护剂和水的计算研究为开发新的冷冻保护剂和优化保存方法提供了宝贵的见解。我们描述了这些复杂系统的分子模拟的快速发展现状，总结了分子尺度的保护和稳定机制，并讨论了激发该领域持续创新的挑战。
