Zhen Zhuo, Potta Thrimoorthy, Christensen Matthew D, Narayanan Eshwaran, Kanagal Kapil, Breneman Curt M, Rege Kaushal
Rensselaer Exploratory Center for Cheminformatics Research and Department of Chemistry and Chemical Biology, Rensselaer Polytechnic Institute, 110 Eighth Street, Troy, New York 12180, United States.
Chemical Engineering, Arizona State University, Tempe, Arizona 85287-6106, United States.
ACS Biomater Sci Eng. 2019 Feb 11;5(2):654-669. doi: 10.1021/acsbiomaterials.8b00963. Epub 2019 Jan 23.
Quantitative approaches to structure-property relationships are critical for the accelerated design and discovery of biomaterials in biotechnology and medicine. However, the absence of definitive structures, unlike those available for small molecules or 3D crystal structures available for some proteins, has limited the development of Quantitative Structure-Property Relationship (QSPR) models for investigating physicochemical properties and biological activity of polymers. In this study, we describe a combined experimental and cheminformatics paradigm for first developing QSPR models of polymer physicochemical properties, including molecular weight, hydrophobicity, and DNA-binding activity. Quantitative Structure-Activity Relationship (QSAR) models of polymer-mediated transgene expression were then developed using these physicochemical properties with an eye towards developing a novel two-step chemical informatics paradigm for determining biological activity (e.g., transgene expression) of polymer properties as related to physicochemical properties. We also investigated a more conventional approach in which biomaterial efficacy, i.e., transgene expression activity, was directly correlated to structural representations of the polymers used for delivering plasmid DNA. Our generalized chemical informatics approach can accelerate the discovery of polymeric biomaterials for several applications in biotechnology and medicine, including in nucleic acid delivery.
结构-性质关系的定量方法对于生物技术和医学中生物材料的加速设计和发现至关重要。然而，与小分子或某些蛋白质的三维晶体结构不同，聚合物缺乏明确的结构，这限制了用于研究聚合物物理化学性质和生物活性的定量结构-性质关系（QSPR）模型的发展。在本研究中，我们描述了一种结合实验和化学信息学的范式，用于首先建立聚合物物理化学性质的QSPR模型，包括分子量、疏水性和DNA结合活性。然后，利用这些物理化学性质建立聚合物介导的转基因表达的定量结构-活性关系（QSAR）模型，旨在开发一种新颖的两步化学信息学范式，以确定聚合物性质与物理化学性质相关的生物活性（如转基因表达）。我们还研究了一种更传统的方法，即生物材料功效（即转基因表达活性）与用于递送质粒DNA的聚合物的结构表示直接相关。我们的通用化学信息学方法可以加速用于生物技术和医学中多种应用（包括核酸递送）的聚合物生物材料的发现。
