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利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 了解蛋白质的柔韧性及其可能的影响因素，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。配基结合和周围水的重排都可能改变蛋白质的灵活性。水对蛋白质的结构、动态和功能特性的贡献是众所周知的，但还没有得到很好的表征。一些被埋藏的水分子可能会使蛋白质基质变得更紧或更具弹性。此外，蛋白质-配体的相互作用必须与与水的相互作用竞争。在这个项目中，我们将对带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，以便定量表征非共价键(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。我们正计划分析稳定性，即在三个不同大小、灵活性和配体结合腔形状的蛋白质系统中形成氢键和疏水接触的速率和动力学。我们还将研究蛋白质突变或配体结合时水动力学和氢键的形成是如何改变的。

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.