EXPANDED PROTEIN STRUCTURE REFINEMENT AND VALIDATION

扩展的蛋白质结构精炼和验证

• 批准号: 6856584
• 负责人: ETHAN A MERRITT
• 金额: $ 21.41万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-03-01 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6856584
• 关键词: Internet; X ray crystallography; automated data processing; bioimaging /biomedical imaging; biotechnology; chemical models; computer simulation; computer system design /evaluation; conformation; high throughput technology; molecular biology information system; molecular dynamics; protein structure; protein structure function; structural biology

Description: (Applicant's abstract) A major goal of the Protein Structure Initiative (Structural Genomics) is to increase the rate of new biological knowledge obtained from protein crystallography, by developing new methods to enhance the efficiency and throughput of structure determination. This proposal addresses several factors limiting the current efficiency. (1) The amount of biological information increases with increasing resolution of the X-ray structure, but full model building and refinement of the highest resolution structures is disproportionately time-consuming. (2) The amount of information from lower resolution structures is limited partly because simplified models are refined to describe these structures. (3) The utility of the database of known structures is limited partly by the reliability of those structures, and the degree to which their interpretation can be automated. This project will develop and distribute computational tools to speed the refinement, improve the quality, and validate the result of protein crystal determinations, with special emphasis on obtaining more information from the increasing number of high resolution structures. Eventual widespread application of these tools will increase the accuracy and information content of a large fraction of all future protein structural models, including those resulting from the Protein Structure Initiative. The key to this work is the use of expanded structural models that include explicit descriptions of atomic anisotropy and modes of molecular vibration. Analysis of near-atomic resolution structures refined with anisotropic displacement parameters will be used to build and maintain a database of statistical properties seen for these parameters in well-refined structures. These properties will be developed as quality control criteria for validating new protein structures. They will also be implemented as restraint targets for structure refinement at lower resolution. This approach should permit incorporation of explicit models for anisotropy into structural models refined at typical resolutions for protein crystallography (about 2A). This, in turn, will make it easier to identify key biological features such as the presence and conformation of bound ligands, and the nature of hinge and inter-domain motions.

描述：（申请人的摘要）蛋白质结构的主要目标 倡议（结构基因组学）是为了提高新生物的比率 通过开发新方法从蛋白质晶体学中获得知识 提高结构测定的效率和通量。这个提议 解决了限制当前效率的几个因素。 (一)金额 生物信息随着 X 射线分辨率的提高而增加 结构，但最高分辨率的完整模型构建和细化 结构非常耗时。 (2)信息量 来自较低分辨率结构的限制部分是因为简化的模型 被细化来描述这些结构。 (3) 数据库的实用性 已知的结构部分地受到这些结构的可靠性的限制，并且 它们的解释可以自动化的程度。该项目将 开发和分发计算工具以加速细化、改进 质量，并验证蛋白质晶体测定的结果， 特别强调从不断增加的数量中获取更多信息 高分辨率结构。这些工具的最终广泛应用将 提高未来很大一部分的准确性和信息内容 蛋白质结构模型，包括由蛋白质结构产生的模型 倡议。这项工作的关键是使用扩展的结构模型 包括原子各向异性和分子模式的明确描述 振动。近原子分辨率结构分析 各向异性位移参数将用于构建和维护 这些参数的统计特性数据库经过精炼 结构。这些特性将被开发为质量控制标准 验证新的蛋白质结构。它们也将作为约束措施实施 以较低分辨率进行结构细化的目标。这种方法应该 允许将各向异性的显式模型合并到结构模型中 以蛋白质晶体学的典型分辨率（约 2A）进行精炼。这，在 转动，将使识别关键的生物学特征变得更容易，例如 结合配体的存在和构象，以及铰链和 域间运动。

项目成果

Structure of ribose 5-phosphate isomerase from Plasmodium falciparum.

恶性疟原虫核糖 5-磷酸异构酶的结构。

• 发表时间: 2006-05-01
• 作者: Holmes, Margaret A;Buckner, Frederick S;Van Voorhis, Wesley C;Verlinde, Christophe L M J;Mehlin, Christopher;Boni, Erica;DeTitta, George;Luft, Joseph;Lauricella, Angela;Anderson, Lori;Kalyuzhniy, Oleksandr;Zucker, Frank;Schoenfeld, Lori W;Ear
• 通讯作者: Ear

A molecular viewer for the analysis of TLS rigid-body motion in macromolecules.

用于分析大分子中 TLS 刚体运动的分子查看器。

• 发表时间: 2005-04
• 作者: Painter, Jay;Merritt, Ethan A
• 通讯作者: Merritt, Ethan A

Cooperative hydrogen bond interactions in the streptavidin-biotin system.

链霉亲和素-生物素系统中的协同氢键相互作用。

• 发表时间: 2006-03
• 作者: Hyre, David E;Le Trong, Isolde;Merritt, Ethan A;Eccleston, John F;Green, N Michael;Stenkamp, Ronald E;Stayton, Patrick S
• 通讯作者: Stayton, Patrick S

Structure of the conserved hypothetical protein MAL13P1.257 from Plasmodium falciparum.

恶性疟原虫保守假设蛋白 MAL13P1.257 的结构。

• 发表时间: 2006-03-01
• 作者: Holmes, Margaret A;Buckner, Frederick S;Van Voorhis, Wesley C;Mehlin, Christopher;Boni, Erica;Earnest, Thomas N;DeTitta, George;Luft, Joseph;Lauricella, Angela;Anderson, Lori;Kalyuzhniy, Oleksandr;Zucker, Frank;Schoenfeld, Lori W;Hol, Wim G J
• 通讯作者: Hol, Wim G J

Electronic Reprint Biological Crystallography Optimal Description of a Protein Structure in Terms of Multiple Groups Undergoing Tls Motion Biological Crystallography Optimal Description of a Protein Structure in Terms of Multiple Groups Undergoing Tls Mot

电子重印 生物晶体学 根据经历 Tls Mot 的多个基团对蛋白质结构的最佳描述 生物晶体学 根据经历 Tls Mot 的多个基团对蛋白质结构的最佳描述

• 发表时间: 2024-09-13
• 作者: J. Painter;E. Merritt
• 通讯作者: E. Merritt