CAREER: Computational and Experimental Design and Engineering of Proteins

John Desjarlais得到了理论和计算化学计划以及分子生物物理计划的资助，以开发和实验评估用于蛋白质设计和工程的计算方法的使用。 算法将开发使用组合优化方法和原子力场的蛋白质设计的评估相结合。 拟议的实验将用于评估设计的变化对蛋白质性质的影响，如稳定性，动力学，结构，最重要的是功能。 目前正在研究的蛋白质是来自枯草芽孢杆菌的冷休克蛋白B，选择它是因为它的小尺寸、易于生产和容易测量的性质。 Desjarlais的教学计划涉及生物物理化学和计算生物学新课程的开发。 这些课程将与宾夕法尼亚州立大学生命科学联盟共同开发和教授。蛋白质设计领域自20世纪80年代成立以来一直在持续发展。 新型蛋白质或天然蛋白质变体的设计、生产和生物物理表征为蛋白质折叠成明确定义的稳定结构所需的氨基酸序列的质量提供了丰富的见解。 最近的发展相结合的计算和实验方法的蛋白质设计开辟了令人兴奋的机会，为未来的蛋白质设计和工程。 这一前景可能最终导致设计新的蛋白质或修改现有蛋白质的性质，如增加热或化学稳定性。 这些努力的成功也将为设计具有治疗或工业价值的纳米技术装置和分子创造新的途径。

John Desjarlais is supported by a grant from the Theoretical and Computational Chemistry Program and the Molecular Biophysics program to develop and experimentally evaluate the use of computational methods for the design and engineering of proteins. Algorithms will be developed using a combination of combinatorial optimization methods and atomistic force fields for the evaluation of protein designs. The proposed experiments will be used to evaluate the effects of designed changes on the properties of proteins such as stability, dynamics, structure, and most importantly, function. The protein currently under investigation is the cold shock protein B from Bacillus subtilis, chosen for its small size, ease of production, and readily measurable properties. Desjarlais' teaching plan involves the development of new courses on Biophysical Chemistry and Computational Biology. The courses will be developed and taught in conjunction with the Penn State University Life Sciences Consortium.The field of protein design has continued to grow since its inception in the 1980's. The design, production, and biophysical characterization of novel proteins or variants of natural proteins has provided a wealth of insight into the qualities of amino acid sequences required for the folding of proteins into well defined, stable structures. Recent developments in the combination of computational and experimental methods for protein design has opened up exciting opportunities for the future of protein design and engineering. This promise may ultimately lead to the design of novel proteins or modification of the properties of existing proteins, such as increased thermal or chemical stability. Success in these efforts will also create new avenues for the design of nanotechnological devices and molecules with therapeutic or industrial value.