Simulating Protein Structures, Complexes, And Dynamics

我们继续在生物分子系统的能量学和动力学的计算研究中开发、实施和应用模拟方法。我们正致力于根据极性、非极性和溶剂结构效应来完善对大分子溶剂化的连续描述。一份手稿已经提交，另一份正在准备中。 我们还基于同源性对蛋白质进行建模，并努力改进此类模型的生成和精炼(Curr。蛋白质Pept.科学，2006；书的章节，在印刷中)。一篇讨论蛋白质表面侧链构象预测的论文正在出版(蛋白质结构。功能。生物信息网，正在出版中)。在与NCI的合作中，我们在遗传性子宫肌瘤病和肾癌的研究中建立了人类富马酸水合酶四聚体的模型(J.Genet.，2006)。在NICHD中，我们借助我们的同源模型(摩尔)研究了人促黄体激素受体突变的生物学效应。内分泌，2006)。与NCI合作，我们一直在研究与Hsp90(摩尔)结合的激酶的相互作用。牢房。Biol.，2006)。 与NIMH和NHLBI合作，我们正在准备一份手稿，描述确定用作脑成像探针的外周苯二氮卓类受体配体过渡状态的可靠方法。目前正在进行量子化学计算，以设计Hsp90的抑制剂，并建立A-β淀粉样蛋白探针的结构-活性关系。在NIDA的帮助下，我们正在研究阿片受体配体的构效关系。 与NICHD一起，我们正在研究与褪黑激素合成有关的蛋白质的动力学和能量学。 与NIDDK合作，我们致力于表征碳纳米管的化学、热力学和光谱性质以及它们与水的相互作用(J.PHY.，2006)。

We have continued to develop, implement, and apply simulation methods in computational studies of the energetics and dynamics of biomolecular systems. We are working to refine a continuum description of macromolecular solvation in terms of polar, nonpolar, and solvent-structure effects. One manuscript has been submitted, and another is in preparation. We also model proteins based on homology and work to improve the generation and refinement of such models (Curr. Protein Pept. Sci., 2006; book chapter, in press). A paper discussing the prediction of side-chain conformations on protein surfaces is in press (Proteins Struct. Funct. Bioinform., in press). In collaboration with NCI, we built a model of the human fumarate hydratase homotetramer in a study of hereditary leiomyomatosis and renal cell cancer (J. Med. Genet., 2006). With NICHD, we studied the biological effect of a mutation in the human luteinizing hormone receptor with the aid of our homology model (Mol. Endocrinol., 2006). With NCI, we have been studying the interactions involved in kinase binding to Hsp90 (Mol. Cell. Biol., 2006). In collaboration with NIMH and NHLBI, we are preparing a manuscript describing reliable ways of determining the transition state of peripheral benzodiazepine receptor ligands that are utilized as probes for brain imaging. Quantum chemical calculations are being carried out to design inhibitors of Hsp90 and to establish a structure-activity relationship for A-beta amyloid probes. With NIDA, we are studying the structure-activity relationships of opioid-receptor ligands. With NICHD we are studying the dynamics and energetics of proteins involved in the synthesis of melatonin. In collaboration with NIDDK, we have worked to characterize the chemistry, thermodynamics, and spectroscopic properties of carbon nanotubes and their interactions with water (J. Chem. Phys., 2006).