摘要：Computational design of proteins is a relatively new field, where scientists search the enormous sequence space for sequences that can fold into desired structure and perform desired functions. With the computational approach, proteins can be designed, for example, as regulators of biological processes, novel enzymes, or as biotherapeutics. These approaches not only provide valuable information for understanding of sequence-structure-function relations in proteins, but also hold promise for applications to protein engineering and biomedical research. In this review, we briefly introduce the rationale for computational protein design, then summarize the recent progress in this field, including de novo protein design, enzyme design, and design of protein-protein interactions. Challenges and future prospects of this field are also discussed.

摘要：新型冠状病毒(SARS-CoV-2)的核衣壳蛋白在其生命周期中起着至关重要的作用,包括与病毒RNA形成核糖核蛋白复合体(RNP).本研究报告了核衣壳蛋白的N端结构域(NTD)和C端结构域(CTD)以及N端结构域-RNA复合物(NTD-RNA)的晶体结构,揭示了NTD独特的四聚体结构,并提出了NTD-RNA复合物中不同的RNA结合模式,这可能有助于RNP的形成.本研究还筛选到了同时是核衣壳蛋白NTD和CTD的小分子抑制剂头孢曲松钠,它可以通过阻断RNA与NTD的结合,抑制RNP的形成,从而阻断SARSCoV-2病毒的生活周期.这些结果有助于后续进一步开展以核衣壳蛋白为靶点的抗病毒药物设计研究.