Protein–protein interactions (PPIs) are important biochemical processes that represent a major challenge in modern biology. Current approaches, which include high-throughput screening and computer aided ligand design, have limitations regarding the identification of hit matter. This current investigation focuses on computational study for protein–protein docking of hypoxia inducible factor-1α (HIF-1α), a tumor inducible factor, and Raf-1 kinase inhibitory protein (RKIP), a tumor metastasis suppressor. These are individually crystallized structures of interacting proteins, which interact to generate a conformational space. HIF activity in pancreatic tumors is determined by hypoxia and HIF-1α subunit availability. RKIP can be used as a prognostic indicator in a number of tumors. The interaction of RKIP with HIF-1α protects against pancreatic cancer (PC) metastasis by inhibiting its hypoxia function. We have explored the binding affinity between both the proteins with the HADDOCK (high ambiguity driven protein–protein docking) server, which determined that 158 structures in 11 clusters represent 79.0% of water-refined models. Of the best 10 clusters, the structures of cluster 2 were found to be better, as they had the lowest Z-score. Further supporting HIF-1α-RKIP interaction, pulldown assay has shown dissociation of RKIP from HIF-1α after CoCl2 treatment in both PC cell lines.

蛋白质-蛋白质相互作用（PPI）是重要的生化过程，代表了现代生物学的主要挑战。当前的方法，包括高通量筛选和计算机辅助配体设计，在鉴定命中物方面存在局限性。这项当前的研究侧重于低氧诱导因子-1α（HIF-1α）（一种肿瘤诱导因子）和Raf-1激酶抑制蛋白（RKIP）（一种肿瘤转移抑制因子）的蛋白-蛋白对接的计算研究。这些是相互作用蛋白的单独结晶的结构，它们相互作用以产生构象空间。胰腺肿瘤中的HIF活性取决于缺氧和HIF-1α亚基的可用性。RKIP可用作许多肿瘤的预后指标。RKIP与HIF-1α的相互作用通过抑制缺氧功能来预防胰腺癌（PC）转移。我们已经使用HADDOCK（高歧义度驱动的蛋白质-蛋白质对接）服务器探索了这两种蛋白质之间的结合亲和力，该服务器确定11个簇中的158个结构代表了79.0％的水精制模型。在最好的10个簇中，发现簇2的结构更好，因为它们的最低Z分数。进一步支持HIF-1α-RKIP相互作用，下拉分析显示在两种PC细胞系中，在CoCl2处理后，RKIP从HIF-1α上解离。