Enhancing Protein Stability and Function by Confinement in Nanoporous Materials: Fundamental Understanding Using Experiments and Simulations

通过纳米多孔材料的限制增强蛋白质稳定性和功能：通过实验和模拟获得基本理解

• 批准号: 0967937
• 负责人: Shekhar Garde
• 金额: $ 38.17万
• 依托单位: Rensselaer Polytechnic Institute
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-03-01 至 2015-02-28
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0967937&HistoricalAwards=false
• 关键词: Enhancing; Protein; Stability; Function; Confinement

0967937CoppensStructural changes of proteins adsorbed on the concave surface of nanoporous silica and othermaterials will be studied to understand how and why confinement affects their catalytic activity and thermal stability. Preliminary experimental investigations on high surface area, ordered nanoporous materials to be considerably extended in this project demonstrate the possibility to adsorb large quantities of several prototypical proteins at a high rate. Most significantly, a considerably increased enzymatic activity and stability was observed, apparently induced by strong interactions between the protein and a solid support whose pores are barely broader than the protein molecules. In order to understand such confinement of the investigators will carry out a systematic program of molecular simulations and calculations based on statistical mechanics, which focuses on systems of increasing complexity from homo and hetero polymers to proteins used in the experimental effort. This understanding is a prerequisite to designing a broad spectrum of applications from healthcare to catalysis, separations, sensing, and controlled release.Intellectual merit: Proteins frequently undergo structural changes when confined to nanopores, or tethered to a surface. These changes, which positively or negatively impact enzyme activity and stability, depend on the support protein pair and the properties of the medium, and remain poorly understood. Development and implementation of statistical mechanical theory aided by high performance computing helps us to gain fundamental understanding on how local curvature, as well as electrostatics, hydrophobicity and hydration influence protein structure, stability and activity in constrained environments. Detailed experimentation on well characterized, carefully synthesized nanoporous materials, with designed pore surface properties, completes the picture obtained by studies on protein adsorption on convex nanostructures, such as nanoparticles and nanotubes. This molecular insight can be incorporated into chemical engineering models of adsorption, diffusion and reaction. Progress on the synthesis of well structured nanomaterials allows validation of theoretical work, but it will also allow leveraging this knowledge to the synthesis of hybrid materials with rationally designed protein support interactions, and offer insights useful to biological systems.Broader impact: Fundamental insights gained by this study on protein confinement in nanoporous materials readily translate to the rational design and synthesis of hybrid nanomaterials that have transformative impact on technological applications varying from enzymatic catalysis and sensors to high throughput, selective (bio-) separations via chromatography and membranes for the production of therapeutics, and biomedical applications. The quantity of (expensive) protein could be reduced, its activity controlled, its stability increased, and recovery facilitated. In addition, this research program offers an enriching educational experience for graduate and undergraduate students. Concepts will be integrated in thermodynamics and reaction engineering classes. Women and underrepresented minorities will be specifically targeted for research participation. The New Visions METS program will be used to involve high school students and attract them to studies in science and engineering. Several female undergraduate students and a high school student were already involved in preliminary work. International exchanges will be strengthened, including collaboration with Dr. Ajayan Vinu at the National Institute of Materials Science (NIMS) in Tsukuba, Japan, in particular for experiments. The Japan Science and Technology Foundation already funded a semester of research at NIMS for one of the PI's graduate students on preliminary experiments in the area of this proposal. The ongoing Molecularium movie project, of which the co-PI is anexecutive producer, brings the world of atoms and molecules to life in an animation on the Big Screen, including a recent IMAX production, based on real molecular simulations

0967937 Coppens将研究吸附在纳米多孔二氧化硅和其他材料凹面上的蛋白质的结构变化，以了解限制如何以及为什么影响其催化活性和热稳定性。对高表面积有序纳米多孔材料的初步实验研究在该项目中得到了相当大的扩展，证明了以高速率吸附大量几种原型蛋白质的可能性。最显著的是，观察到酶活性和稳定性显著增加，这显然是由蛋白质与其孔仅比蛋白质分子宽的固体支持物之间的强相互作用引起的。为了理解这种局限性，研究人员将进行基于统计力学的分子模拟和计算的系统程序，该程序侧重于从同质和异质聚合物到实验中使用的蛋白质的日益复杂的系统。这种理解是设计从医疗保健到催化、分离、传感和控制释放的广泛应用的先决条件。智力优势：蛋白质在被限制在纳米孔中或被束缚在表面时经常发生结构变化。这些变化，积极或消极地影响酶的活性和稳定性，取决于支持蛋白对和介质的性质，仍然知之甚少。高性能计算辅助下的统计力学理论的发展和实施有助于我们对局部曲率以及静电，疏水性和水合作用如何影响蛋白质结构，稳定性和受限环境中的活性获得基本的理解。详细的实验充分表征，精心合成的纳米多孔材料，与设计的孔表面性能，完成了蛋白质吸附的凸纳米结构，如纳米粒子和纳米管的研究所获得的图片。这种分子洞察力可以被纳入吸附，扩散和反应的化学工程模型。在合成结构良好的纳米材料方面取得的进展可以验证理论工作，但它也将允许利用这些知识来合成具有合理设计的蛋白质支持相互作用的杂化材料，并提供对生物系统有用的见解。本研究对蛋白质在纳米多孔材料中的限制所获得的基本见解很容易转化为杂化纳米材料的合理设计和合成其对从酶催化和传感器到高通量、通过色谱和膜进行选择性（生物）分离以生产治疗剂和生物医学应用的技术应用具有变革性影响。可以减少（昂贵的）蛋白质的量，控制其活性，增加其稳定性，并促进回收。此外，该研究计划为研究生和本科生提供了丰富的教育经验。概念将被整合在热力学和反应工程类。妇女和代表性不足的少数民族将被专门针对研究参与。新视野METS计划将用于吸引高中生参与，吸引他们学习科学和工程。几名女大学生和一名高中生已经参与了初步工作。将加强国际交流，包括与日本筑波国家材料科学研究所的Ajayan Vinu博士合作，特别是在实验方面。日本科学技术基金会已经为PI的一名研究生在NIMS进行了一个学期的研究，以进行该提案领域的初步实验。正在进行的分子电影项目，其中的合作PI是一个执行制片人，带来了世界的原子和分子的生活在动画的大屏幕上，包括最近的IMAX制作，基于真实的分子模拟