MOLECULAR DYNAMIC SIMULATION OF THE INTERACTION OF THE ADAPTER WITH THE GENETIC

适配器与遗传相互作用的分子动力学模拟

• 批准号: 7601312
• 负责人: MARIA G KURNIKOVA
• 金额: $ 0.03万
• 依托单位: CARNEGIE-MELLON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-01 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7601312
• 关键词: Affect; Binding; Computer Retrieval of Information on Scientific Projects Database; DNA Sequence Rearrangement; Drug Design; Free Energy; Funding; Genetic; Grant; Graph; Hydrogen Bonding; Institution; Ligand Binding; Ligands; Modeling; Mutation; Personal Satisfaction; Pliability; Property; Proteins; Rate; Research; Research Personnel; Resources; Shapes; Source; System; United States National Institutes of Health; Water; covalent bond; molecular dynamics; nanoengineering; protein function; size

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Understanding protein flexibility and factors that may affect it is important for predicting of protein function and building a functional model applicable in drug design or bio-nano-engineering. Both ligand binding and rearrangement of surrounding water may alter protein flexibility. Contribution of water to the structural, dynamic, and functional properties of proteins is well known but not well characterized. Some buried water molecules may tighten the protein matrix or make it more flexible. Also protein-ligand interactions must compete with interaction with water. In this project we will perform Molecular Dynamics simulations of proteins with ligands, and calculate free energy differences upon protein mutation or ligand binding in order to quantitatively characterize how stability of non-covalent bonds (hydrogen bonds and hydrophobic contacts) alters protein flexibility. Flexibility of the protein will be assessed via recently proposed graph theoretical approach. We are planning to analyze stability, i.e. rates and dynamics of formation and breakage of hydrogen bonds and hydrophobic contacts in three protein systems that differ by size, flexibility, and a shape of ligand-binding cavities. We will also study how water dynamics and hydrogen-bond formation is altered upon protein mutation or binding of a ligand.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 了解蛋白质的柔韧性和可能影响其的因素对于预测蛋白质功能和构建适用于药物设计或生物纳米工程的功能模型很重要。周围水的配体结合和重排可能会改变蛋白质柔韧性。水对蛋白质的结构，动态和功能特性的贡献是众所周知的，但没有很好的特征。一些埋入的水分子可能会拧紧蛋白质基质或使其更灵活。蛋白质 - 配体相互作用也必须与与水相互作用竞争。在该项目中，我们将对具有配体的蛋白质进行分子动力学模拟，并计算蛋白质突变或配体结合时的自由能差，以定量地表征非共价键（氢键和疏水接触）如何改变蛋白质的稳定性。将通过最近提出的图理论方法评估蛋白质的灵活性。我们计划分析稳定性，即在三种因大小，柔韧性和配体结合腔的形状不同的氢键和疏水接触的形成和破裂的速率和动力学。我们还将研究蛋白质突变或配体结合后水动力学和氢键形成如何改变。