针对细胞因子-细胞因子受体（CK-CKR）相互作用的治疗药物会破坏细胞信号传导，并可有效治疗包括肿瘤在内的许多疾病。然而，缺乏对 CK/CKR 上带注释的结构表面区域的普遍且快速的访问，限制了结构驱动方法在开发靶向大分子药物和精准医学疗法方面的进展。在此，我们开发了 CytoSIP（单核苷酸多态性 (SNP)、界面和表型），这是一个丰富的互联网应用程序，基于实验确定的 CK/CKR 结构复合物中热点周围原子相互作用的数据库。 CytoSIP 包含： (1) CK/CKR 上的 SNP； (2)涉及CK/CKR结构域的相互作用，包括CK/CKR界面、寡聚界面、表位或其他药物靶向表面； (3) 与 CK/CKR 或 SNP 相关的疾病和表型。该数据库框架引入了独特的三级 SIP 数据模型，使用蛋白质结构（复合物）作为基础框架（分子水平），将遗传变异（原子水平）与疾病表型（有机体水平）联系起来。采用定制的筛选工具来检索相关的 CK/CKR 子集，这减少了询问涉及 CK/CKR 表面热点和相关病理的大型数据集所需的时间和资源。 CytoSIP 门户可通过 https://CytoSIP.biocloud.top 公开访问，促进对 CK/CKR 之间的上下文相关串扰和靶向治疗药物的开发进行全景研究。© 2024。作者。

Therapeutic agents targeting cytokine-cytokine receptor (CK-CKR) interactions lead to the disruption in cellular signaling and are effective in treating many diseases including tumors. However, a lack of universal and quick access to annotated structural surface regions on CK/CKR has limited the progress of a structure-driven approach in developing targeted macromolecular drugs and precision medicine therapeutics. Herein we develop CytoSIP (Single nucleotide polymorphisms (SNPs), Interface, and Phenotype), a rich internet application based on a database of atomic interactions around hotspots in experimentally determined CK/CKR structural complexes. CytoSIP contains: (1) SNPs on CK/CKR; (2) interactions involving CK/CKR domains, including CK/CKR interfaces, oligomeric interfaces, epitopes, or other drug targeting surfaces; and (3) diseases and phenotypes associated with CK/CKR or SNPs. The database framework introduces a unique tri-level SIP data model to bridge genetic variants (atomic level) to disease phenotypes (organism level) using protein structure (complexes) as an underlying framework (molecule level). Customized screening tools are implemented to retrieve relevant CK/CKR subset, which reduces the time and resources needed to interrogate large datasets involving CK/CKR surface hotspots and associated pathologies. CytoSIP portal is publicly accessible at https://CytoSIP.biocloud.top , facilitating the panoramic investigation of the context-dependent crosstalk between CK/CKR and the development of targeted therapeutic agents.© 2024. The Author(s).