The development of quantum computing-based biomolecular recognition methods for use by researchers at all stages of the translational pathway

工作计划将包括在每年的研究中，在项目的实验（UCL）和计算（Evotec， UCL）元素之间进行迭代。在拟议的项目中，将进行四种不同的FMO应用：第一年：FMO- espc（静电电位互补）-静电相互作用对生物分子识别至关重要。FMO和ESPC之间的集成（FMO-ESPC）将能够精确计算配体和蛋白质之间的静电电位互补（ESPC），从而确定对SBDD至关重要的关键相互作用点。第2年：FMO-PPI（蛋白质-蛋白质相互作用）-蛋白质-蛋白质相互作用（ppi）对蛋白质功能至关重要。据报道，在人类相互作用中有超过645,000种与疾病相关的PPI，但这些药物靶点中只有2%被PPI调节剂解决。我们将整合fmo和PPI （FMO-PPI）来识别对蛋白质-蛋白质结合（热点）至关重要的残基，从而促进基于结构的PPI调节剂（sdd -PPI）的药物设计。第三年：fmo -停留时间-我们已经开发了一种精确的方法来计算药物停留时间使用操纵分子动力学。我们将整合片段分子轨道（SMD/FMO） G蛋白偶联受体的计算建模，以一种可以自动化和缩放的方式用于高端计算系统。第4年：开发供生物医学研究人员使用的在线FMO工作流

The work plan will involve iteration between experimental (UCL) and computational (Evotec, UCL) elementsof the project throughout each of the years of study. Four different FMO applications will be pursued duringthe proposed project:Year 1: FMO-ESPC (electrostatic potential complementarity) - The role of electrostatic interactions isvital for biomolecular recognition. Integration between FMO and ESPC (FMO-ESPC) will enable theaccurate calculation of the electrostatic potential complementarity (ESPC) between a ligand and the proteinto identify key interaction points critical for SBDD.Year 2: FMO-PPI (Protein-protein interactions) - Protein-protein interactions (PPIs) are essential forprotein functions. More than 645,000 disease-relevant PPIs have been reported in the human interactomehowever only 2% of these drug targets have been addressed with PPI modulators. We will integrate FMOand PPI (FMO-PPI) to identify residues that are critical for protein-protein binding (hotspots) thus facilitatingstructure-based drug design of PPI modulators (SBDD-PPI).Year 3: FMO-Residence Time - We have developed an accurate means of calculating drug residence timeusing steered molecular dynamics. We will integrate Fragment Molecular Orbital (SMD/FMO) computationalmodelling for G protein-coupled receptors in a way that can be automated and scaled for use on high-endcomputing systems.Year 4: Development of an online FMO Workflow for use by biomedical researchers