Abstract：
Integrins are heterodimeric glycoproteins crucial to the physiology and pathology of many biological functions. As adhesion molecules, they mediate immune cell trafficking, migration, and immunological synapse formation during inflammation and cancer. The recognition of the vital roles of integrins in various diseases revealed their therapeutic potential. Despite the great effort in the last thirty years, up to now, only seven integrin-based drugs have entered the market. Recent progress in deciphering integrin functions, signaling, and interactions with ligands, along with advancement in rational drug design strategies, provide an opportunity to exploit their therapeutic potential and discover novel agents. This review will discuss the molecular modeling methods used in determining integrins\' dynamic properties and in providing information toward understanding their properties and function at the atomic level. Then, we will survey the relevant contributions and the current understanding of integrin structure, activation, the binding of essential ligands, and the role of molecular modeling methods in the rational design of antagonists. We will emphasize the role played by molecular modeling methods in progress in these areas and the designing of integrin antagonists.
摘要：
整合素是对许多生物学功能的生理学和病理学至关重要的异二聚体糖蛋白。作为粘附分子，它们介导免疫细胞运输，迁移,炎症和癌症期间的免疫突触形成。对整合素在各种疾病中的重要作用的认识揭示了它们的治疗潜力。尽管在过去的三十年里付出了巨大的努力，到现在为止,只有七种基于整合素的药物进入市场。解密整合素功能的最新进展，信令,以及与配体的相互作用，随着合理药物设计策略的进步，提供了一个机会来利用他们的治疗潜力和发现新的药物。这篇综述将讨论用于确定整合素的动态特性以及提供在原子水平上理解其特性和功能的信息的分子建模方法。然后，我们将调查相关贡献和目前对整合素结构的理解，激活,基本配体的结合，以及分子建模方法在合理设计拮抗剂中的作用。我们将强调分子建模方法在这些领域的进展和整联蛋白拮抗剂的设计中所起的作用。
