Abstract:

Galectin-10 (Gal10) exists in human eosinophils and can undergo phase transformation into crystals to induce asthma. The molecular interactions between Gal10 protein and antibody were investigated by molecular dynamics simulation combined with molecular mechanics-Poisson Boltzmann surface area free energy decomposition. It is found that the binding of antibody on Gal10 protein was mainly driven by hydrophobic interaction. The most favorable amino acid residues for binding were Y69, K117, D113, E68, I116, H114 of Gal10 protein and W53-H, Y104-H, N97-L, K55-L, Y93-L, R100-H of antibody. Then an affinity combination model for the molecular interactions between Gal10 protein and antibody was proposed. A sequence WXYXXNXY was then designed for constructing a library of inhibitors, followed by the screening using molecular docking, molecular dynamics simulation, conformational comparison, etc. Finally, WGYGWNGY was obtained and identified as a potentially effective asthma inhibitor.

Key words: protein, peptide, molecular simulation, interface, inhibitor

摘要：

Galectin-10（Gal10）存在于人类嗜酸性细胞中，可经历相变成为晶体而诱发哮喘疾病。通过分子动力学模拟方法结合分子力学-泊松-玻尔兹曼方程-表面积计算自由能分解方法解析Gal10蛋白与溶晶抗体相互作用，发现Gal10蛋白与溶晶抗体结合主要依靠疏水相互作用驱动，对结合起最有利贡献的氨基酸残基包括Gal10蛋白的Y69、K117、D113、E68、I116、H114和溶晶抗体的W53-H、Y104-H、N97-L、K55-L、Y93-L、R100-H。以此为基础，构建Gal10蛋白与溶晶抗体相互作用的亲和结合模型，以设计抑制剂并构建序列为WXYXXNXY的抑制剂库，利用分子对接、分子动力学模拟、构象比对等方法，最终确定获得WGYGWNGY等潜在高效哮喘抑制剂。

关键词: 蛋白质, 肽, 分子模拟, 界面, 抑制剂