The SSIP approach to protein-ligand complex interactions

蛋白质-配体复合物相互作用的 SSIP 方法

• 批准号: 2468566
• 金额: --
• 依托单位: University of Cambridge
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2468566
• 关键词: SSIP; approach; protein; ligand; complex

Year 1: Generic training activities for all first-year student members of the CDT.Year 2-4: The field of drug discovery faces a dichotomy. It is possible to screen high volume of small molecules but algorithms that do are empirically parametrised and quantify non-covalent interactions. To obtain high quality detail takes a substantial amount of time, skill, and computing power. Both high volume and high quality algorithms, however, use an energy predictor and an optimisation tool that leads the search to equilibrium. We will develop a Surface Site Interaction Point model that uses DFT-calculated detail in quick quantification of interactions. It reliably describes the interaction patterns present between molecules. It reliably predicts solvation energies, and in considering protein-ligand complexes, it can describe non-covalent interactions within a conformation without a need for explicit solvent treatment. Here we show such an approach gives good estimates of binding affinities using a common dataset - CASF-2016. We can predict and quantify interactions present in a complex, therefore providing a path to systematic drug candidate optimisation. If coupled with an optimisation algorithm, this new approach could form a tool for screening ligands, thus yielding a unified approach to drug design that is both swift and accurate.

第一年：CDT 所有一年级学生成员的通用培训​​活动。第二年至第四年：药物发现领域面临着二分法。筛选大量小分子是可能的，但这样做的算法是根据经验参数化并量化非共价相互作用。要获得高质量的细节需要大量的时间、技能和计算能力。然而，大容量和高质量算法都使用能量预测器和优化工具来引导搜索达到平衡。我们将开发一个表面站点交互点模型，该模型使用 DFT 计算的细节来快速量化交互。它可靠地描述了分子之间存在的相互作用模式。它可靠地预测溶剂化能，并且在考虑蛋白质-配体复合物时，它可以描述构象内的非共价相互作用，而不需要明确的溶剂处理。在这里，我们展示了这种方法使用通用数据集 - CASF-2016 可以很好地估计结合亲和力。我们可以预测和量化复合物中存在的相互作用，从而提供系统候选药物优化的途径。如果与优化算法相结合，这种新方法可以形成一种筛选配体的工具，从而产生一种既快速又准确的统一药物设计方法。