TAILIEUCHUNG - Báo cáo khoa học: Combinatorial approaches to protein stability and structure

Why do proteins adopt the conformations that they do, and what determines their stabilities? While we have come to some understandingof the forces that underlie protein architecture, a precise, predictive, physicochemical explanation is still elusive. Two obstacles to addressing these questions are the unfathomable vastness of protein sequence space, and the difficulty in makingdirect phy-sical measurements on large numbers of protein variants. Here, we review combinatorial methods that have been applied to problems in protein biophysics over the last 15 years. The effects of hydrophobic core composition, the most important determinant of structure and stabil-ity, are still poorly understood. . | Eur. J. Biochem. 271 1595-1608 2004 FEBS 2004 doi MINIREVIEW Combinatorial approaches to protein stability and structure Thomas J. Magliery1 and Lynne Regan1 2 1 Department of Molecular Biophysics Biochemistry and department of Chemistry Yale University New Haven CT USA Why do proteins adopt the conformations that they do and what determines their stabilities While we have come to some understanding ff the forces llial Uddrrlie protein architecture a precise predictive physicochemical explanation is still elusive. Two obstacles to addressing these questions are the unfathomable vastness of protein sequence space and the difficulty in making direct pyy-sical measurements on large numbers of protein variants. Here we review combinatorial methods that have been applied to problems in protein biophysics over the last 15 years. The effects of hydrophobic core composition the most important determinant of structure and stability are still poorly understood. Particular attention is given to core composition as addressed by library methods. Increasingly useful screens and selections in combination with modern high-throughput approaches borrowed from genomics and proteomics efforts are makingthe empirical statistical correlation between sequence and structure a tractable problem for the comingyears. Introduction Understanding the htisis of protein ttabiliyv and ttrectLire is a problem of fundamental chemical and physical significance. In addition such knowledge is critical for numerous biomedical applications includingbut not limited to the preparation of stable protein-based therapeutics and the treatment of pathologies related to mutated unstable proteins 1-4 . The importance of this issue has led to considerable study at least since the first protein crystal structures were determined 5-7 . In spite of such attention a satisfactory understandingof how proteins adopt the conformations that they do is still far from complete. Why has it .

• Báo cáo khoa học
• Report medicine
• traditional medicine
• scientific reports
• Crystal structure
• medical analysis
• biochemical studies
• medical knowledge
• medical research
• analysis of cytoplasmic
• oxidation
• bacteria
• hemoglobin
• medicine
• cell proliferation
• breast cancer
• chemical reaction
• gastric cancer
• hormone medicine
• tumor cells
• environmental medicine