CONFORMATIONALLY CONSTRAINED PROTEIN POLYMERS

拟议的研究将需要设计、建模、合成和表征含有非天然氨基酸的重复多肽序列。特别强调的是蛋白质聚合物的体内表达，包括蛋氨酸类似物同丙基甘氨酸，或“Hag”。这些聚合物中存在的烯烃化学功能将被用于创造具有定制性能的新型大分子材料。编码含有重复i到i + 4模式Hag残基的α -螺旋蛋白聚合物的人工基因将在大肠杆菌蛋氨酸营养不良菌中表达。纯化后，Hag侧链的末端烯烃基团将进行合环复分解。该反应将产生19元环大环，将蛋白质的二级结构束缚在一起。预期的产品是一种单分散的刚性棒聚合物。该聚合物的生物物理和材料性质将被研究，特别关注α -螺旋结构的热稳定性。聚合物的行为将通过分子动力学模拟来模拟。这些聚合物的表征将通过新化学功能的精确空间模式为材料科学提供进步，并将通过加强对控制蛋白质二级结构形成的力的理解，为蛋白质生物物理学提供进步。

The proposed research will entail the design, modeling, synthesis, and characterization of repeating polypeptide sequences incorporating non-natural amino acids. A particular emphasis will be the in vivo expression of protein polymers that include the methionine analog homoallylglycine, or "Hag". The presence of the alkene chemical functionality in these polymers will be exploited to create novel macromolecular materials with tailored properties. Artificial genes encoding alpha-helical protein polymers that include Hag residues in a repeating i to i + 4 pattern will be expressed in an E. coli methionine auxotroph. Following purification, the terminal alkene groups of the Hag sidechains will be subjected to ring-closing metathesis. This reaction will generate 19-membered ring macrocycles that will tether the protein secondary structure. The anticipated product is a monodisperse rigid-rod polymer. The biophysical and materials properties of this polymer will be investigated, with particular attention to the thermal stability of the alpha- helical structure. The behavior of the polymers will be modeled by molecular dynamics simulations. Characterization of these polymers will provide advances in materials science through the precise spatial patterning of novel chemical functionalities, and will provide advances in protein biophysics through an enhanced understanding of the forces that control the formation of protein secondary structure.