MOLECULAR MODELLING OF PROTEIN-LIGAND INTERACTIONS

总体目标是了解各种化学物质的化学特性， 生物受体系统及其与小分子生物活性物质的相互作用 配体。 本研究项目旨在初步了解 控制特异性识别的生理化学和大分子规则 以及使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。 的 目标将使用理论和实验分子 我们将使用抗体-配体结合位点作为 受体-配体相互作用的范例。 模拟生物受体 位点，就其立体特异性识别和配体结合而言， 可以作为研究互动和充满活力的模型 配体和受体的成分。 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 结晶学 这项研究是第一次使用这两种方法 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 受体-配体相互作用的研究， 生物活性配体和受体可以以合理和 预测的方式。

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.