T-4 Lysozyme as a Model for Protein Folding

该项目的目标是更详细地了解蛋白质结构、稳定性和动力学之间的相互关系。T4溶菌酶为模型蛋白。这种中等大小的蛋白质具有已知的三维结构。该溶菌酶存在许多突变蛋白，其热力学稳定性受其组成的调节。达奎斯特博士开发了一种质粒表达系统可以高效地产生大量的同位素取代蛋白。他将使用现代核磁共振来研究这类蛋白质。蛋白质如何折叠的问题被认为是现代分子生物学中最重要也是最不为人所知的问题之一。如果能够详细了解特定氨基酸序列折叠成特定形状的原因以及序列变化如何改变该形状、其热力学稳定性及其与其他配体的相互作用潜力，将大大提高许多相关领域的研究水平。随着对折叠问题的理解的进步，工程蛋白产品的复杂性相应增加，可以从序列数据中更可靠地预测结构。

The goal of this project is to understand in greater detail the interrelationships of protein structure, stability and dynamics. T4 lysozyme is the protein used as a model. This moderate sized protein has a known 3-dimensional structure. Many mutant proteins of this lysozyme exist whose thermodynamic stability is modulated by the composition. Dr. Dahlquist has developed a plasmid expression system which allows large amounts of isotopically substituted protein to be produced efficiently. He will use modern nuclear magnetic resonance to study such proteins. The question of how proteins fold is acknowledged as one of the most important and least understood of modern molecular biology. A number of related areas would be greatly enhanced by the ability to understand in detail why a particular amino acid sequence folds into a particular shape and how changes in sequence change that shape, its thermodynamic stability and its interaction potential with other ligands. Progress in the understanding of the folding problem may allow more reliable predictions of structure from sequence data with a corresponding increase in the sophistication of engineered protein products.