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 Rensselaer Polytechnic Institute is to design peptides using rational and combinatorial approaches with the aim of controlling the shape and growth of crystals. Engineering crystal shape and size using peptides is a challenging problem that requires fundamental understanding of water-mediated peptide-crystal interactions. To this end, this research will use a powerful combination of experiments, molecular modeling, and simulation methods. Calcium oxalate monohydrate crystals will be the material of interest and focus on the discovery and design of peptides that inhibit its growth. Combinatorial approaches based on phage screening will be employed to explore and harness the vast chemical and structural space of peptides. In parallel, the project will use molecular simulations of selected peptides to advance the rational design of them. Using these peptides, this project will study structural features of growing crystals using scanning probe microscopy, which will provide insights into peptide-crystal interactions and enable the design of more effective peptide growth modifiers. These advances will not only lead to the design of drugs for the removal of kidney stones, but potentially transform the philosophy and approach to crystal engineering in the fields of advanced materials for energy, separation, and catalysis. The researchers of this project are dedicated to the education and outreach to the broader public, to attracting women and underrepresented minorities to STEM careers, and using innovative approaches such as Molecularium movies in reaching mass audiences.The broad goal of this proposal is to design peptides that inhibit the growth of calcium oxalate monohydrate crystals, which are implicated in kidney stone formation. The proposed work could enable the design and discovery of novel and effective therapeutics for kidney stones. Incidence of kidney stones is high in the U.S., and growing in the developing world. This project will use high-throughput design of peptides, computer modeling, and specialized microscopy techniques to study the growth of crystals in the presence of peptides. The proposed approaches are expected to discover not only potential peptide therapeutics for the removal of kidney stones, but may uncover the fundamental mechanisms of the kidney stone formation, which will mark a significant advance in our understanding of stone therapy. The scientific principles that emerge from this work may also lead to therapeutics for other diseases (e.g., vascular plaques, gallstones, gout, osteoarthritis, etc). Understanding of crystal shape engineering may also lead to new paradigms for advanced materials design with applications in catalysis and energy. Other goals of this project are equal commitment to the education of a skilled technical and scientific workforce, high-school children, and broad public. This project is dedicated in attracting women and underrepresented minorities to STEM careers, and developing innovative outreach approaches such as the Molecularium 3D-IMAX movies in attracting younger generation to science and technology.