大分子聚集结构的小角X光散射和计算机模拟研究

Behind the frontier studies in quantitative structure-activity relationships, rational design of advanced delivery systems, ultra-fine filtration membranes and nano-scale lithography patterning technologies etc., quantification of the aggregation of macromolecules, either synthetic polymers or biomacromolecules, is of key importance. We will integrate theoretical calculation, computer simulation, small angle X-ray scattering together with statistical approaches to systematically explore the hierarchical structures in macromolecular aggregates. Quantitative information from the interactions, conformations, aggregates to phase domains are extracted and understood from thermodynamic and kinetic aspects. Specially, the correlation of the entanglement of polymer chains, the self-aggregation of proteins and their resulted patterns experienced exact processing will be investigated. The adsorption, orientation and unfolding of proteins at the vicinity of polymer membranes with different distributions in roughness, composition, polarity and charged patches will be correlated. Through these two exact systems, the methodologies to steadily deliver quantitative structure information based on solution small angle X-ray scattering are developed and applied. We further integrate either the two-dimensional scattering pattern or the one-dimension scattering intensity profile into the energy functions that guiding molecular simulations. Such integration can facilitate the convergence of simulation towards statistically real structure as revealed from scattering. In this way, we aim to extend the general force field and the biased adjustment so to describe the aggregation of macromolecules with sufficient university and accuracy. Such enhanced force field together with simulation strategies will be developed for the prediction of structure characteristics and scattering patterns, based on big data analysis.

定量剖析含高分子和生物大分子体系的聚集行为及其聚集体的多层次结构，对于明确生物活性的分子机制、研发先进的控释输运体系、支撑精细膜分离和纳米图案化技术等具有重要意义。基于小角X光散射结构信息的深层次挖掘，利用理论计算、分子模拟结合大数据分析，明晰分子间相互作用和构象协同变化聚集的动力学和热力学特征；针对蛋白质与高分子复合体系，研究分子链缠结和自聚集等大分子聚集行为对溶液及其固化结构的影响规律；研究在具有不同粗糙度、基团和电荷分布的高分子表界面上，蛋白质解折叠、取向和吸附行为；发展基于溶液小角X光散射曲线纳米尺度的结构信息解析算法，将散射曲线作为能量函数引导计算机模拟的平衡态结构收敛，阐述特征结构形成的热力学和动力学机制，建立偏倚的力场模型，为研究大分子聚集体的复杂结构提供定量解析方法；利用大数据扩展和模型验证，为未知体系的大分子聚集结构和散射特征进行预测，促进先进材料的研发。

围绕蛋白质复合物和高分子膜材料的聚集行为和聚集结构，利用小角X光散射、计算机模拟和大数据研究结合，探索了多个体系的组成工艺决定结构和定量结构性质关系。对于蛋白-小分子复合物，明晰了非特异性溶剂诱导的蛋白变性过程，与分子对接、生物活性测定结合厘清了活性小分子对酶活性抑制的分子机理；对于蛋白-大分子复合物，通过与流变、电纺丝耦合，给出了结构调控因素的作用机制和定量联系，为开发蛋白质基生物材料提供了重要参考。在高分子材料体系，定量解析了全氟磺酸离子聚合物的分散液和溶胀膜聚集结构，发现了聚集体特征尺寸的标度关系，为理解特定膜结构形成和调控，膜的结构性质关系提供了依据；进一步与分子动力学模拟和大数据结合，阐明了高分子链构象演化、水分子在高分子致密膜中的受限输运、以及膜组成工艺结构与包含力学、传导、渗漏、溶胀等性质的定量联系。开发出polySML软件平台，可为高分子材料结构和性质的预测和设计提供可实践的方案决策参考。资助期间发表含J. Mater. Chem. A, J. Membr. Sci., ACS Appl. Mater. Inter.等论文13篇，申请授权软件著作权2项，受邀做国际国内会议口头报告5次，培养博士和硕士研究生各1名。

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