小柯机器人

美国加州大学伯克利分校Ting Xu团队开发出基于群体的异质聚合物设计来模拟蛋白质的混合物。该研究于2023年3月8日在线发表于国际一流学术期刊《自然》。

研究人员提出，除了已知的单体序列要求外，蛋白质序列还在片段水平上编码了多对相互作用，以导航随机相遇；能够模仿这种相互作用的合成异质聚合物可以复制蛋白质在生物液体中单独和集体的行为。研究人员从天然蛋白质库中提取了化学特征和沿蛋白质链在节段水平上的顺序排列，并利用这些信息来设计无序、部分折叠和折叠蛋白质的混合物的异构聚合物组合。对于每个异质聚合物组合，与天然蛋白质的节段相似程度决定了其复制生物液体的许多功能的能力，包括在翻译过程中协助蛋白质折叠，在不冷藏的情况下保存胎牛血清的活力，增强蛋白质的热稳定性，以及在生物相关条件下表现得像合成细胞液。分子研究进一步将蛋白质序列信息在片段水平转化为具有确定范围、多样性程度和时空可用性的分子间相互作用。这个框架为合成实现蛋白质特性、设计生物/仿生混合材料以及最终实现物质到生命的转变提供了宝贵的指导原则。

据介绍，生物流体是最复杂的混合体，其成分不断变化，不能被分子定义。尽管有这些不确定性，蛋白质还是按照程序波动、折叠、功能和演化。

附：英文原文

Title: Population-based heteropolymer design to mimic protein mixtures

Author: Ruan, Zhiyuan, Li, Shuni, Grigoropoulos, Alexandra, Amiri, Hossein, Hilburg, Shayna L., Chen, Haotian, Jayapurna, Ivan, Jiang, Tao, Gu, Zhaoyi, Alexander-Katz, Alfredo, Bustamante, Carlos, Huang, Haiyan, Xu, Ting

Issue&Volume: 2023-03-08

Abstract: Biological fluids, the most complex blends, have compositions that constantly vary and cannot be molecularly defined1. Despite these uncertainties, proteins fluctuate, fold, function and evolve as programmed2,3,4. We propose that in addition to the known monomeric sequence requirements, protein sequences encode multi-pair interactions at the segmental level to navigate random encounters5,6; synthetic heteropolymers capable of emulating such interactions can replicate how proteins behave in biological fluids individually and collectively. Here, we extracted the chemical characteristics and sequential arrangement along a protein chain at the segmental level from natural protein libraries and used the information to design heteropolymer ensembles as mixtures of disordered, partially folded and folded proteins. For each heteropolymer ensemble, the level of segmental similarity to that of natural proteins determines its ability to replicate many functions of biological fluids including assisting protein folding during translation, preserving the viability of fetal bovine serum without refrigeration, enhancing the thermal stability of proteins and behaving like synthetic cytosol under biologically relevant conditions. Molecular studies further translated protein sequence information at the segmental level into intermolecular interactions with a defined range, degree of diversity and temporal and spatial availability. This framework provides valuable guiding principles to synthetically realize protein properties, engineer bio/abiotic hybrid materials and, ultimately, realize matter-to-life transformations.

DOI: 10.1038/s41586-022-05675-0

Source: https://www.nature.com/articles/s41586-022-05675-0

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html