MOLECULAR MODELING OF PROTEIN/LIGAND INTERACTIONS

蛋白质/配体相互作用的分子建模

• 批准号: 2022500
• 负责人: SCOTT D LINTHICUM
• 金额: $ 25.41万
• 依托单位: TEXAS A&M UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-05-01 至 2001-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2022500
• 关键词: X ray crystallography; antibody; antibody specificity; antigen antibody reaction; chemical binding; chemical kinetics; chemical models; chemical structure function; computer simulation; conformation; fluorescence spectrometry; humoral immunity; intermolecular interaction; ligands; molecular dynamics; molecular site; nuclear magnetic resonance spectroscopy; physical model; protein sequence; receptor binding; site directed mutagenesis; stereochemistry; thermodynamics

The overall objective is to understand the chemical specificity of various biological receptor systems and their interactions with small bioactive ligands. This research project seeks to gain a preliminary insight into the physiochemical and macromolecular rules governing specific recognition and binding of bioactive ligands using modern molecular biology, biophysical measurements and supramolecular computational chemistry. The objective will be accomplished using theoretical and experimental molecular modelling studies in which we will use antibody-ligand binding sites as an exemplar of receptor-ligand interactions. Mimicry of biological receptor sites, in terms of their stereospecific recognition and binding of ligands, can serve as a model for the study of interactive and energetic constituents of both the ligand and receptor. We will use quantitative structure-activity ligand binding techniques, fluorescence spectroscopy techniques, gene sequencing and site-directed mutagenesis procedures, computer-aided modelling and dynamics simulations, and x-ray crystallography. This study is the first of its kind to use both theoretical and experimental approaches to characterize receptor binding sites for bioactive ligands. It is imperative that we understand the basis of receptor-ligand interactions so that strategies in designing new bioactive ligands and receptors may be developed in a rational and predictive manner.

总体目标是了解各种物质的化学特异性 生物受体系统及其与小生物活性物质的相互作用 配体。 该研究项目旨在初步了解 控制特定识别的物理化学和大分子规则 以及利用现代分子生物学结合生物活性配体， 生物物理测量和超分子计算化学。 这 目标将通过理论和实验分子来实现 我们将使用抗体-配体结合位点作为模型研究 受体-配体相互作用的范例。 生物受体的模仿 位点，就其立体特异性识别和配体结合而言， 可以作为交互和能量研究的模型 配体和受体的组成部分。 我们将使用定量 结构-活性配体结合技术、荧光光谱 技术、基因测序和定点诱变程序， 计算机辅助建模和动力学模拟以及 X 射线 晶体学。 这项研究是同类研究中第一个同时使用这两种方法的研究 表征受体结合的理论和实验方法 生物活性配体的位点。 我们必须了解基础 受体-配体相互作用的研究，以便设计新的策略 可以合理地开发生物活性配体和受体 预测方式。