SCIENTIFIC TESTING OF NMR STRUCTURE DETERMINATION SCHEME

核磁共振结构测定方案的科学测试

• 批准号: 3498705
• 负责人: EVA MEIROVITCH
• 金额: $ 5万
• 依托单位: BIOSYM TECHNOLOGIES, INC.
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-07-01 至 1992-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3498705
• 关键词: DNA binding protein; blood proteins; computer program /software; computer simulation; computer system design /evaluation; macromolecule; mathematics; molecular dynamics; nuclear magnetic resonance spectroscopy; nucleic acid hybridization; plant proteins; protein structure; trypsin inhibitors

DESCRIPTION: (Adapted from Applicant's Abstract) The objective of this proposal is to carry out the scientific testing associated with a new NMR software package developed currently at Biosym, namely an integrated theoretical/computational tool for determining molecular structures from NMR data. The scheme combines an elaborate NMR Relaxation Matrix Approach (IRMA) with various molecular modeling formulations such as Distance Geometry (DG), Restrained Molecular Dynamics (RMD)/Restrained Energy Minimization (REM) and Dynamical Simulated Annealing (DSA). Structure determination proceeds by first `generating' a structure, with an extended version of T. Havel's metric matrix formulation called DG II or with a recently proposed DSA scheme, which has been implemented at Biosym using the molecular dynamics (MD) package DISCOVER. This is followed by structure refinement, pursued using a DISCOVER-integrated version of IRMA. The integrity and validity of this complex system is contingent upon careful scientific testing aimed at assessing limitations (on one hand) and relative advantages of alternative components (on the other). Moreover, the unique scientific rigor inherent in this system will be fully appreciated only if we can illustrate its ability to solve momentarily ambiguous molecular structures. DG II and the DISCOVER-based DSA will be evaluated comparatively using as test cases crambin and ZnIV fingerlike domain. Limitations and benefits of the two techniques will be pinpointed by subjecting bovine pancreatic trypsin inhibitor (BPTI) to a detailed investigation and comparing the results with previous studies. A sensitivity test of IRMA will be performed using the alpha-amylase inhibitor Tendamistat. The important implications of treating internal motions, to the extent that previous structural ambiguities can be resolved by properly accounted for dynamic phenomena, will be illustrated by re-investigating Neutrophil Peptide 5. The merit of this research in terms of technological innovation and commercial value will be borne out by a scientifically sound, novel, unique and very useful tool for elucidating NMR structures.

描述：（改编自申请人的摘要）本发明的目的是 一项建议是进行与新的核磁共振相关的科学测试 Biosym目前开发的软件包，即集成的 一种理论/计算工具，用于从 NMR数据。 该方案结合了一个精心设计的核磁共振弛豫矩阵方法 （IRMA）与各种分子建模公式，如距离 几何（DG）、约束分子动力学（RMD）/约束能量 最小化（REM）和动态模拟退火（DSA）。 结构 确定通过首先“生成”一个结构来进行， T的版本。Havel的度量矩阵公式称为DG II或具有 最近提出的DSA方案，已在Biosym使用 分子动力学（MD）软件包DISCOVER。 这之后是 结构优化，使用DISCOVER集成版本的IRMA进行。 这个复杂系统的完整性和有效性取决于 仔细的科学测试旨在评估局限性（一方面）， 替代组件的相对优势（另一方面）。 此外，委员会认为， 这一系统所固有的独特的科学严谨性将充分 只有当我们能够说明它的能力， 模糊的分子结构 DG II和基于DISCOVER的DSA将 比较评估使用作为测试用例crambin和ZnIV fingerlike 域 这两种技术的局限性和优点将被指出 通过对牛胰胰蛋白酶抑制剂（BPTI）进行详细 调查和比较结果与以往的研究。 一 将使用α-淀粉酶进行IRMA的敏感性测试 抑制剂Tendamistat。 治疗内分泌疾病的重要意义 运动，在一定程度上，以前的结构模糊性可以解决 通过适当地解释动力学现象，将由 重新研究神经肽5 这项研究的价值在于 技术创新和商业价值将得到证明， 科学合理，新颖，独特，非常有用的工具， NMR结构。