科学家实现小分子结合蛋白的从头设计 作者: 发布时间:/9/6 14:16:33 美国加州大学旧金山分校William F. DeGrado、Nicholas F. Polizzi等研究人员实现小分子结合蛋白的从头设计。相关论文于9月4日发表在《科学》杂志上。
为了进行结合蛋白的计算设计,研究人员开发了蛋白质结构单元(van der Mer,vdM),该算法将每个氨基酸的骨架映射到相互作用化学基团的统计优选位置。使用vdM,研究人员设计了六个从头蛋白来结合药物阿哌沙班,其中两个具有亚微摩尔的结合亲和力。 X射线晶体学和诱变证实了具有精确设计空腔的结构,从而能够在药物-蛋白质复合物中形成了良好的相互作用。vdM可以设计用于感知、医学和催化的功能蛋白。 附:英文原文 Title: A defined structural unit enables de novo design of small-molecule binding proteins
Author: Nicholas F. Polizzi, William F. DeGrado
Issue Volume: /09/04
Abstract: The de novo design of proteins that bind highly functionalized small molecules represents a great challenge. To enable computational design of binders, we developed a unit of protein structure a van der Mer (vdM) that maps the backbone of each amino acid to statistically preferred positions of interacting chemical groups. Using vdMs, we designed six de novo proteins to bind the drug apixaban; two bound with low and submicromolar affinity. X-ray crystallography and mutagenesis confirmed a structure with a precisely designed cavity that forms favorable interactions in the drug protein complex. vdMs may enable design of functional proteins for applications in sensing, medicine, and catalysis.
DOI: 10.1126/science.abb8330
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期刊信息 Science:《科学》,创刊于1880年。隶属于美国科学促进会,最新IF:41.037官方网址:投稿链接: