Collaborative Research: Design of Peptide Crystal Growth Modifiers Using Experiments and Simulations

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This award by the Biomaterials program in the Division of Materials Research to University of Houston focuses on developing fundamental understandings of peptide interactions with surfaces of calcium oxalate monohydrate crystals, a predominant component of human kidney stones. This project will use a synergistic combination of peptide synthesis, materials characterization, and molecular simulations to develop rational design approaches that tailor calcium oxalate monohydrate crystallization. This collaborative proposal between the University of Houston and Rensselaer Polytechnic Institute will utilize the vast chemical and structural space of peptides to discover effective modifiers of calcium oxalate monohydrate crystal growth. This project proposes a high-throughput approach to screen peptide libraries, whereby the most potent candidates will be investigated by scanning probe microscopy to quantify peptide-crystal interactions and molecular modeling to investigate peptide binding to crystal surfaces. The overarching goal of this proposed research is to establish peptide-mediated crystallization as a versatile platform to achieve predictable and tunable structures and/or properties. To this end, the project is expected to advance our understanding of peptide-calcium oxalate monohydrate interactions, and will be transformative in that the philosophy and approach could be applied to crystal and shape engineering of other materials. Developments from this proposed research may lead to the identification of potent calcium oxalate monohydrate growth inhibitors as viable drug targets for kidney stone disease. Moreover, this award will be used to strengthen outreach initiatives at the K-12, undergraduate, and graduate levels to promote science education and research. This investigator will work with KIPP Houston High School (a minority institution) to establish a program that uses the research supported by this award to promote increased interest and participation in STEM.Crystal engineering is a challenging area of research where advancements in rational design can impact the development of biomimetic systems, therapeutics, and advanced materials. This proposed research project focuses on designing peptides that interact with surfaces of calcium oxalate monohydrate crystals, which are one of the most common constituents of human kidney stones. This is a prototypical example of calcification, which is ubiquitous in many biological and physiological processes. The key intellectual contribution of this project will be to bring to bear unique, yet highly synergistic, expertise to quantify fundamental principles of peptide-crystal interactions. Through a combination of experiments and modeling, this research team will identify which peptides most effectively inhibit calcium oxalate monohydrate crystal growth, and determine which among these candidates exhibit an affinity for binding to specific surfaces of these crystals to enable the tailoring of crystal properties (e.g. size and shape). Rational design of peptide sequences combined with high-throughput screening will allow us to discover the most effective modifiers of the crystal growth, which can potentially lead to the identification of drug targets for kidney stones to address rising worldwide incidence rates of stone disease. General principles of crystal inhibitor design from this project could lead to developments in therapeutics for other diseases, and new methods for improving advanced materials. The integration of crystal engineering with medicine will be used as a tool to promote STEM education at the K-12 level and encourage students to become more active in research projects. The team members will work with local high school students and teachers to offer hands-on research opportunities, present guest lectures on engineering topics to Advanced Placement Chemistry students, develop lesson plans that integrate basic concepts of crystallization, and present seminars to discuss career opportunities in STEM fields.