Hsp27 是小热休克蛋白 (sHSP) 的成员，小热休克蛋白是已知的针对异常蛋白质折叠行为的细胞防线。然而，它的上调与多种病理性疾病有关，包括几种类型的癌症。神经酰胺合酶 (CerS) 介导神经酰胺的合成，神经酰胺是一种关键的结构和信号脂质。从功能上讲，下游神经酰胺代谢物与细胞凋亡过程有关，其异常功能与抗癌耐药性有关。研究表明，CerS1 可能被 Hsp27 抑制，从而在体外产生生化抗癌作用。然而，这种蛋白质-蛋白质相互作用（PPI）的性质尚未在分子方面进行大量研究，因此，我们首次使用分子动力学模拟描述了 CerS1-Hsp27 相互作用的动态图谱。时间尺度分子动力学模拟分析表明，系统范围内的构象事件包括稳定性降低、灵活性增加、致密性降低和 CerS1 折叠减少。结合能分析显示界面处有 56 个残基，总稳定能为-158 KJ/mol，存在良好的相互作用。与蛋白质骨架相比，CerS1 催化结构域经历了相反的趋势。然而，根据 DCCM 和 DSSP 分析，这些残基采用了高度紧凑的构象。此外，构成基质穿梭机制的保守残基（SER 212、ASP 213、ALA 240、GLY 243、ASP 319）表现出显着的刚性，这意味着神经酰胺前体的进入和组装受到限制；因此，这是一种可能的抑制机制。该报告的发现将有助于更好地从分子角度理解 CerS1-Hsp27 相互作用，并破译其通往未探索的抗癌机制和治疗的潜在途径。

Hsp27 is a member of the small heat-shock proteins (sHSPs) - the known cellular line of defence against abnormal protein folding behaviors. Nevertheless, its upregulation is linked to a variety of pathological disorders, including several types of cancers. The ceramide synthases (CerS) mediate the synthesis of ceramide, a critical structural and signaling lipid. Functionally, downstream ceramide metabolites are implicated in the apoptosis process and their abnormal functionality has been linked to anticancer resistance. Studies showed that CerS1 are possibly inhibited by Hsp27 leading to biochemical anticancer effects in vitro. Nevertheless, the nature of such protein-protein interaction (PPI) has not been considerably investigated in molecular terms, hence, we present the first description of the dynamics CerS1-Hsp27 interaction landscapes using molecular dynamics simulations. Time-scale molecular dynamics simulation analysis indicated a system-wide conformational events of decreased stability, increased flexibility, reduced compactness, and decreased folding of CerS1. Analysis of binding energy showed a favorable interaction entailing 56 residues at the interface and a total stabilizing energy of -158 KJ/mol. The CerS1 catalytic domain experienced an opposite trend compared to the protein backbone. Yet, these residues adopted a highly compact conformation as per DCCM and DSSP analysis. Furthermore, conserved residues (SER 212, ASP 213, ALA 240, GLY 243, ASP 319) comprising the substrate shuttling machinery showed notable rigidity implying a restrained ceramide precursor access and assembly; hence, a possible inhibitory mechanism. Findings from this report would streamline a better molecular understanding of CerS1-Hsp27 interactions and decipher its potential avenue toward unexplored anti-cancer mechanisms and therapy.