COMPLEX FORMATION AND BINDING AFFINITY OF NHERF1 TO C-TERMINAL PEPTIDES

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 使用分子动力学（MD）模拟和计算蛋白质修饰，我们将表征PDZ-配体复合物的Na/H交换调节因子-1（NHERF 1），由于其生物学和医学的重要性。我们将研究PDZ 1/PDZ 2-配体相互作用。为了探测这种相互作用，我们将使用来自NaPi协同转运蛋白（NATRL; L1）、PTH受体（WETVM; L2）或NHERF 1（LFSNL; L3）的五个氨基酸残基羧基末端识别基序。我们将估计PDZ 1对L1和L2的结合亲和力以及PDZ 2对L2和L3的结合亲和力。通过结合分离的PDZ结构域的分子建模，将提出串联PDZ 1-PDZ 2的模型。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Using Molecular Dynamic (MD) simulations and computational protein modification, we will characterize PDZ-ligand complexes of the Na/H Exchange Regulatory Factor-1 (NHERF1) due to their biological and medicinal importance. We will investigate the PDZ1/PDZ2-ligand interactions. To probe such interactions we will use the five amino acid residue carboxy-terminal recognition motifs from the NaPi cotransporter (NATRL; L1), PTH receptor (WETVM; L2) or NHERF1(LFSNL; L3). We will estimate the binding affinity of PDZ1 for both L1 and L2 and PDZ2 for L2 and L3. By combining molecular modeling of isolated PDZ domains, a model for tandem PDZ1-PDZ2 will be proposed.