High-Accuracy Protein Models Derived from Lower Resolution Data

从较低分辨率数据得出的高精度蛋白质模型

• 批准号: 7931242
• 负责人: Andrzej Kloczkowski
• 金额: $ 5.2万
• 依托单位: IOWA STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7931242
• 关键词: Amino Acid Sequence; Area; Arts; Behavior; Bioinformatics; Biology; CASP6 gene; Carbon; Categories; Cellular biology; Cereals; Chemistry; Code; Collaborations; Communicable Diseases; Communities; Computer Simulation; Computers; Consensus; Crystallography; Data; Databases; Detection; Development; Drug Design; Ensure; Enzymes; Evaluation; Foundations; Future; Generations; Genes; Genetic; Genomics; Goals; Guidelines; High Performance Computing; Homology Modeling; Individual; Institutes; International; Investments; Iowa; Laboratories; Lead; Letters; Machine Learning; Mathematics; Medal; Methodology; Methods; Metric; Mining; Modeling; Molecular; Molecular Biology; Molecular Conformation; Molecular Models; Monsters; Motion; Organism; Peptide Sequence Determination; Performance; Pharmaceutical Preparations; Physics; Polishes; Principal Investigator; Procedures; Protein Structure Initiative; Proteins; Protocols documentation; Public Health; Research; Research Personnel; Research Project Grants; Resolution; Sampling; Solutions; Source; Staging; Structural Models; Structure; Techniques; Testing; Torsion; Universities; Ursidae Family; Validation; Variant; Wisconsin; Work; base; comparative; computer science; data mining; database structure; experience; improved; insertion/deletion mutation; member; method development; molecular mechanics; molecular modeling; network models; novel strategies; numb protein; programs; protein structure; protein structure prediction; quantum; quantum chemistry; reconstruction; research study; restraint; scaffold; simulation; software development; structural biology; theories; three dimensional structure; tool; web site

An outstanding international interdisciplinary team has been assembled that will bring a broad variety of expertise to bear on protein model building, bringing together researchers from chemistry, physics, computer science, mathematics, structural biology, and bioinformatics. The expertise ranges from quantum chemistry to machine learning, and from datamining to high performance computing. Input from collaborating NMR and crystallographers will be essential for validating the protein models. Improving abilities to model proteins can impact public health in important ways by enhancing our basic understanding of protein behavior and by facilitating a more efficient selection of protein targets for drug design. The overall goal is to improve a wide range of protein modeling approaches, both by developing new approaches, and by combining those previously been developed. The specific aims are to: 1) Improve existing comparative (homology) modeling and 2) Improve models obtained by fold-recognition and ab initio procedures to make them useful for molecular replacement. There will be some new methods development. Efforts are in four areas - databases, interaction potentials, conformational sampling, and optimization for combining approaches. We will develop ways to include constraints mined from sub-atomic resolution protein structures using a new HIRES Database (to include structures with resolution < 0.85 A). These will include a structure fragment database, as well as short-range distance distributions. These data can be used to compare modeled structures against the collected data. Uses of the high resolution data will ilclude selecting higher quality fragments to replace poor quality segments in the models, for mining interaction potentials, and as a source of a variety of other high quality information regarding protein structures. Better assessments of protein structural models will be developed, including the assessment of the quality of individual segments within a protein structure; the new metrics developed will be used for assessing the quality of computer-built models, crystal structures and NMR structures, and provide indicators of the expected quality of whole protein models as well as of its segments. New ways to sample protein motions will be pursued. Combining diverse methods will lead to significant gains in the computer modeling of protein structures. Extensive testing and validation will be carried out at each stage and in each part of the project to ensure large gains in model accuracy.

一个优秀的国际跨学科团队已经组装，将带来各种各样的 专业知识承担蛋白质模型的建立，汇集了来自化学，物理，计算机， 科学、数学、结构生物学和生物信息学。专业知识包括量子化学 到机器学习，从数据挖掘到高性能计算。来自合作NMR的输入， 晶体学家将是验证蛋白质模型的关键。提高蛋白质建模的能力可以 通过增强我们对蛋白质行为的基本理解， 有助于更有效地选择用于药物设计的蛋白质靶点。总体目标是改善一个广泛的 一系列蛋白质建模方法，无论是通过开发新的方法，并结合这些方法， 以前开发的。具体目标是：1）改进现有的比较（同源）建模 和2）改进通过折叠识别和从头计算程序获得的模型，使其对以下方面有用： 分子置换会有一些新的方法发展。在四个方面作出了努力-数据库， 相互作用势，构象采样和优化组合方法。我们将开发 包括使用新的HIRES从亚原子分辨率蛋白质结构中挖掘的约束的方法 数据库（包括分辨率< 0.85 A的结构）。这将包括一个结构片段数据库， 以及短程距离分布。这些数据可用于比较建模结构 与收集到的数据进行对比。高分辨率数据的使用将包括选择更高质量的碎片， 替换模型中质量差的片段，用于挖掘相互作用潜力，并作为各种 关于蛋白质结构的其他高质量信息。更好地评估蛋白质结构模型 将开发，包括蛋白质结构内单个片段的质量评估; 开发的新指标将用于评估计算机构建的模型，晶体结构 和NMR结构，并提供整个蛋白质模型的预期质量的指标，以及其 片段将寻求对蛋白质运动进行采样的新方法。结合不同的方法将导致 在蛋白质结构的计算机建模方面取得了重大进展。广泛的测试和验证将 在项目的每个阶段和每个部分都进行了评估，以确保大幅提高模型的准确性。

项目成果

Knowledge-based versus experimentally acquired distance and angle constraints for NMR structure refinement.

基于知识与实验获得的 NMR 结构细化距离和角度约束。

• DOI: 10.1142/s0219720008003448
• 发表时间: 2008
• 期刊: Journal of bioinformatics and computational biology
• 影响因子: 1
• 作者: Cui,Feng;Jernigan,Robert;Wu,Zhijun
• 通讯作者: Wu,Zhijun

A putative mobile genetic element carrying a novel type IIF restriction-modification system (PluTI).

• DOI: 10.1093/nar/gkp1221
• 发表时间: 2010-05
• 期刊: Nucleic acids research
• 影响因子: 14.9
• 作者: Khan F;Furuta Y;Kawai M;Kaminska KH;Ishikawa K;Bujnicki JM;Kobayashi I
• 通讯作者: Kobayashi I

MetaMQAP: a meta-server for the quality assessment of protein models.

• DOI: 10.1186/1471-2105-9-403
• 发表时间: 2008-09-29
• 期刊: BMC bioinformatics
• 影响因子: 3
• 作者: Pawlowski M;Gajda MJ;Matlak R;Bujnicki JM
• 通讯作者: Bujnicki JM

Conformation of a plasmid replication initiator protein affects its proteolysis by ClpXP system.

质粒复制起始蛋白的构象影响 ClpXP 系统的蛋白水解作用。

• DOI: 10.1002/pro.68
• 发表时间: 2009
• 期刊: Protein science : a publication of the Protein Society
• 作者: Pierechod,Marcin;Nowak,Agnieszka;Saari,Anna;Purta,Elzbieta;Bujnicki,JanuszM;Konieczny,Igor
• 通讯作者: Konieczny,Igor

TRACER. A new approach to comparative modeling that combines threading with free-space conformational sampling.

示踪剂。

• 发表时间: 2010
• 期刊: Acta biochimica Polonica
• 影响因子: 1.7
• 作者: Trojanowski,Sebastian;Rutkowska,Aleksandra;Kolinski,Andrzej
• 通讯作者: Kolinski,Andrzej