REFINEMENT OF FOLDED PROTEIN STRUCTURES

折叠蛋白质结构的细化

• 批准号: 6280237
• 负责人: MATTHEW R LEE
• 金额: $ 1.33万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-07-01 至 1999-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6280237
• 关键词: biological products; biomedical resource

In a collaboration with the Dill group at UCSF, I am working on the ab initio protein structure prediction of small proteins (< 100 amino acids) such as CMTI and endothelin. Starting with the low resolution end point structure of our collaborators' folding algorithms, I use molecular dynamics to perform high resolution conformational sampling in search of the native structure, which we predict to be at the global minimum of our force field. Although homology modelling and threading are postulated to be successful in overall fold prediction within the next decade, and despite the great promise shown by folding algorithms, these techniques clearly lack sufficient detail at the molecular level that will allow structure prediction to have significant practical application. Of interest are the b inding pockets and active sites, where small structural differences lead to notable change in protein activity. Given a successful two-step method that accurately determines the macro- and microscopic structures of proteins, the pharmaceutical industry will benefit tremendously in its efforts to produce therapeutic drugs that are needed to modify protein activity. The Computer Graphics Laboratory has proven to be a valuable tool in enabling me to better analyze my data. I frequently use the visualization software package MidasPlus to look at my protein structures. I have also used the hardware to run other applications that display the trajectories of my dynamics simulations. The CGL staff is a helpful resource as well with their programming expertise.

在与加州大学旧金山分校的迪尔小组合作中，我正在研究