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

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 了解蛋白质的柔性及其影响因素，对于预测蛋白质的功能和建立适用于药物设计或生物纳米工程的功能模型具有重要意义。配体结合和周围水的重排都可以改变蛋白质的柔性。水对蛋白质的结构、动力学和功能性质的贡献是众所周知的，但还没有很好地表征。一些隐藏的水分子可能会使蛋白质基质变紧或使其更灵活。此外，蛋白质-配体相互作用必须与水的相互作用竞争。在这个项目中，我们将进行蛋白质与配体的分子动力学模拟，并计算蛋白质突变或配体结合时的自由能差异，以定量表征非共价键（氢键和疏水接触）的稳定性如何改变蛋白质的灵活性。蛋白质的灵活性将通过最近提出的图论方法进行评估。我们计划分析稳定性，即在三种蛋白质系统中氢键和疏水接触的形成和断裂的速率和动力学，这些蛋白质系统的大小，灵活性和配体结合腔的形状不同。我们还将研究水动力学和氢键的形成如何在蛋白质突变或配体结合时改变。

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.