Department of Pharmaceutical Sciences, University of Connecticut, Storrs, CT, 06269, USA.
Department of Mechanical Engineering, University of Connecticut, Storrs, CT, 06269, USA.
Sci Rep. 2018 Jan 16;8(1):849. doi: 10.1038/s41598-017-18151-x.
Rational drug design is the process of finding new medication that can activate or inhibit the biofunction of a target molecule by binding to it and forming a molecular complex. Here, shape and charge complementarities between drug and target are key. To help find effective drug molecules out of a huge pool of possibilities, physical and computer aided tools have been developed. Former offers a tangible experience of the molecular interactions yet lacks measurement and evaluation capabilities. Latter enables accurate and fast evaluations, but does not deliver the interactive tangible experience of physical models. We introduce a novel hybrid model called "Assemble-And-Match" where, we enhance and combine the unique features of the two categories. Assemble-And-Match works based on fabrication of customized molecular fragments using our developed software and a 3D printer. Fragments are hinged to each other in different combinations and form flexible peptide chains, conformable to tertiary structures, to fit in the binding pocket of a (3D printed) target molecule. Through embedded measurement marks, the molecular model is reconstructed in silico and its properties are evaluated. We expect Assemble-And-Match tool can enable combination of visuospatial perception with in silico computational power to aid research and education in drug design.
理性药物设计是通过与靶标分子结合形成分子复合物来寻找能够激活或抑制靶标生物功能的新药物的过程。在这里，药物和靶标之间的形状和电荷互补性是关键。为了帮助从大量可能性中找到有效的药物分子，已经开发出了物理和计算机辅助工具。前者提供了分子相互作用的实际体验，但缺乏测量和评估能力。后者能够进行准确和快速的评估，但不能提供物理模型的交互实际体验。我们引入了一种称为“组装-匹配”的新型混合模型，其中我们增强和结合了这两类的独特功能。“组装-匹配”基于使用我们开发的软件和 3D 打印机制造定制分子片段。片段以不同的组合相互铰接，并形成灵活的肽链，符合三级结构，以适应（3D 打印）靶标分子的结合口袋。通过嵌入式测量标记，分子模型在计算机上进行重建，并评估其性质。我们期望“组装-匹配”工具能够将空间感知与计算机上的计算能力相结合，以辅助药物设计的研究和教育。
