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VISUALIZING THOUSAND-DIMENSIONAL CHEMICAL DIVERSITY

可视化千维化学多样性

基本信息

批准号：
2759830
负责人：
DAVID E PATTERSON
金额：
$ 6.69万
依托单位：
CERTARA USA, INC.
依托单位国家：
美国
项目类别：
财政年份：
1998
资助国家：
美国
起止时间：
1998-09-01 至 1999-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/2759830
关键词：
chemical information system computer graphics /printing computer program /software computer system design /evaluation drug design /synthesis /production imaging /visualization /scanning mathematical model

项目摘要

This application proposes work related to NIMH research topic number 1J. Commercialization by Tripos in both commercial diversity software and in collaborative drug discovery research is very likely. Combinatorial chemistry and high throughput screening provide results at remarkably high rates. However, individual data points are of low quality. Scientists must include their own judgment to prioritize synthesis suggestions from "black boxes," which compute diversity in abstract mathematical spaces of molecular metrics. To do so requires new methods to illustrate important structures in high dimensions by translating them to interpretable graphic displays. Drug discovery is based on the intuitive idea that similar compounds tend to have similar biological effects. A corollary of this "neighborhood behavior" principle is that, if a metric space is valid, active molecules should be clustered within it. However, all metrics documented to be generally valid have roughly 1000 dimensions. The objective of the proposed research is to provide interactive 3D computer graphics displays which represent higher dimensional spaces by preserving the important local distances (nearest neighbor compound clusters). While the development will include heuristics specific to chemistry of drug-like organic compounds, the result may be useful for visualizing key aspects of arbitrary multidimensional data spaces. PROPOSED COMMERCIAL APPLICATION Pharmaceutical companies currently buy Tripos software containing mathematical algorithms for diversity. They license the Optiverse screening library of compounds designed for optimal diversity. Tripos is also involved in collaborative drug discovery projects. Each of these current commercial applications will be improved by use of the visualization tools this project will produce. Potentially the results can be extended to create a new cheminformatics software package and serve as a basis for new bioinformatics offerings as well.

本申请提出了与 NIMH 研究主题 1J 相关的工作。 Tripos 在商业多样性软件和在合作药物发现研究中很有可能。组合化学和高通量筛选提供结果以非常高的比率。然而，个别数据点的含量较低质量。科学家必须包括自己的判断来确定优先顺序来自“黑匣子”的综合建议，计算多样性分子度量的抽象数学空间。为此需要说明高维重要结构的新方法将它们转换为可解释的图形显示。药物发现是基于相似的化合物往往具有相似的直观想法生物效应。这种“邻里行为”的必然结果原则是，如果度量空间有效，活性分子应该聚集在其中。然而，所有记录的指标通常都是 valid 大约有 1000 个维度。拟议研究的目标是提供交互式 3D 计算机图形显示，通过以下方式表示更高维度的空间保留重要的局部距离（最近邻化合物簇）。虽然开发将包括特定于类药物有机化合物的化学，结果可能对可视化任意多维数据空间的关键方面。拟议的商业应用制药公司目前购买的 Tripos 软件包含多样性的数学算法。他们授权 Optiverse 为实现最佳多样性而设计的化合物筛选库。特里普斯还参与合作药物发现项目。这些中的每一个当前的商业应用将通过使用来改进该项目将产生的可视化工具。可能的结果可以扩展以创建新的化学信息学软件包也可作为新生物信息学产品的基础。