COMPUTATIONAL STUDY OF LIGAND PROTEIN INTERACTION: HIV STRUCT BASED DRUG DESIGN

配体蛋白相互作用的计算研究：基于 HIV 结构的药物设计

• 批准号: 6119180
• 负责人: Jian Wang
• 金额: $ 0.54万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-07-01 至 2000-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6119180
• 关键词: AIDS; biomedical resource; immunology; infection; inflammation; lymphatic system; technology /technique; virus

Our research is in structure-based drug design including flexible ligand docking and estimation of ligand binding affinities. Ranking ligand binding affinity is still an unsolved issue in the field of computer-aided drug design. Although we know energy components contributed to binding free energy, we don't know yet how to balance these components to obtain a reliable estimation of the binding free energy. We extensively use the software developed in the Computer Graphics Laboratory to visualize the ligand binding structure, to understand where we made mistakes in our approaches and further more, to improve our energy functions to predict ligand-protein binding free energies. So far we have developed a flexible docking protocol to predict best binding modes for large flexible ligand with more than 16 rotatable bonds. We have proposed a interaction free energy based method to estimate binding free energies. Several pilot calculations show encouraging results.

我们的研究是基于结构的药物设计，包括柔性 配体对接和配体结合亲和力的估计。 排名 配体结合亲和性仍然是免疫学领域中未解决的问题。 计算机辅助药物设计 虽然我们知道能量成分 贡献了束缚自由能，我们还不知道如何平衡 这些组件，以获得一个可靠的估计结合免费 能源 我们广泛使用计算机中开发的软件 图形实验室可视化配体结合结构， 了解我们在方法上的错误所在，并进一步了解， 来改善我们的能量功能， 能量 到目前为止，我们已经开发了一个灵活的对接协议， 预测大于16的大柔性配体的最佳结合模式 可旋转债券 我们提出了一个基于相互作用自由能的 方法来估计结合自由能。 几个试点计算 取得了令人鼓舞的成果。