AREA I BIOMOLECULAR STRUCTURE & FUNCTION: AIDS

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。第一领域的主要目标是阐明生物分子的结构和功能，目的是理解和解释它们在发育和细胞事件中的功能。在为期五年的续期中，一项重要的新举措是在x射线衍射领域招募一名新教员，以确定蛋白质结构，并为该设施提供启动资金。我们要求聘请一名x射线晶体学家的动机是需要补充和加强正在进行的核磁共振结构工作。我们还获得了由诺华公司捐赠的x射线晶体学设备，该设备由学院资助在CCNY的新Pathways生物信息学和生物技术中心建立。生物化学和结构生物学的最新发展允许区域I的成员进一步扩展他们的研究领域到大分子和大分子组装。为了提高生产力和竞争力，他们必须开发新技术，并将核磁共振技术与核磁共振设施结合起来，这些核磁共振设施是纽约市结构生物学中心不可或缺的一部分，该中心于2002年12月16日在我们的校园正式开放。为了实现这一目标，我们在i区增加了一名核磁共振波谱专家Ronnie Ghose博士。这一招聘在我们上次的拨款更新中得到了RCMI的批准。他开发了一个令人兴奋的独立研究项目，并获得了校外资助。他积极地与第一区域的所有成员以及其他区域的成员进行互动。我们的设备在不断改进和更新。在过去的一年里，在马沙克科学楼的广场层交付了一台500兆赫和一台600兆赫的光谱仪，并投入使用。这些机器的费用由学院和RCMI分摊。这种新功能将质谱法进一步扩展到大而脆弱的分子中，并使该工具可供生物科学研究人员使用。Barbara Zajc在RCMI基金的当前资助期内受聘于生物有机化学领域。她研究氟作为生物活性调节剂掺入后的dna -致癌物偶联物，并监测这些修饰导致的结构变化。我们的中心设施现在有两个分子动力学磷光成像仪和一个分子动力学激光密度计，这些对RCMI的每个人都很有用。第一区教师的成就和研究重点大多数第一区教师（Balogh-Nair, Ghose, Gunner, Lazaridis, Schulz, Tasayco, Zajc）得到了外部资助。Schulz博士被邀请撰写题为“真核生物中脂肪酸的氧化”的一本书章节，他在NIH的医学生物化学研究部任职。Gunner博士获得了50万美元的总统科学家和工程师早期职业奖（PECASE）。Balogh-Nair博士（化学）从事树状大分子的合成，对嗜m型HIV-1病毒株具有增强的活性。与传统聚合物相比，树状大分子是独特的核-壳结构，具有三个基本的建筑成分：(a)核，(b)由重复分支细胞单位组成的壳内部（生成），以及(c)末端官能团，即外壳或外围。Ghose博士专注于开发和实施新型核磁共振技术，以探测生物分子的结构和动力学。他还对破译src信号通路中关键酶的结构-功能关系感兴趣。他最近在生物分子核磁共振杂志上发表了一篇关于探测蛋白质慢相关运动的新型核磁共振方法的论文。Gunner博士（生物物理学）是RCMI的一名雇员，他的工作是(a)开发工具来分析和比较蛋白质中带电基团的能量，(b)分析电子和质子的功能，其中侧链或底物电离状态对功能很重要，(c)调查蛋白质结构数据库以确定稳定埋藏电荷的基元。在过去的一年里，Lazaridis博士在膜蛋白建模方面迈出了一大步，他开发了一种有效的脂质双层蛋白质能量功能，作为他的EEF1水溶液能量功能的延伸。Schulz博士（生物化学）的主要目标是提供对不饱和脂肪酸和羟基脂肪酸的b-氧化特别需要的反应和辅助酶的详细了解。Tasayco博士（生物化学）是RCMI的一名员工，他在生物化学上发表了一篇开创性的论文，使用差示扫描量热法识别互补无序蛋白质片段家族中具有残余结构的区域。她目前正在通过核磁共振光谱研究蛋白质未折叠状态下的残余结构，为蛋白质能量学的预测提供基准。Zajc博士研究化学致癌领域的构效关系（SAR）。具体而言，她正在通过氟作为生物活性调节剂的位点特异性掺入对dna -致癌物偶联物进行SAR研究，以评估这种修饰后发生的结构变化。

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. The major Area I goals are to elucidate the structures and functions of biological molecules with the aim of understanding and explaining their functions in development and in cellular events. A major new initiative for the five-year renewal is to recruit a new faculty member in the area of X-ray diffraction for the determination of protein structure and to provide startup funds to equip this facility. Our request for the hire of an X-ray crystallographer is motivated by the need to complement and enhance the ongoing structural work carried out by NMR. We have also secured X-ray crystalography equipment which was donated by Novartis and set up through funds from the college in the new Pathways Bioinformatics and Biotechnology Center at CCNY. Recent developments in biochemistry and structural biology allow members of Area I to further expand their areas of study into large macromolecules and macromolecular assemblies. To be more productive and competitive, they must exploit the new technologies and turn to increased use of NMR techniques in conjunction with the NMR facilities that are integral to the New York City Structural Biology Center that officially opened on our campus December 16, 2002. In accord with this goal we have added a specialist in NMR spectroscopy, Dr. Ronnie Ghose, to Area I. This hire was approved by RCMI in our last grant renewal. He has developed an exciting independent research program and has secured extramural funding. He actively interacts with all members of Area I and members of other areas as well. Our equipment is continually being improved and up-dated. During the past year one 500 and one 600 MHz spectrometers were delivered and put into service on the Plaza Level of the Marshak Science Building. The cost for these machines was split between the College and the RCMI. This new capability expands the use of mass spectrometry further into large and fragile molecules and makes this tool available to researchers in the biological sciences. Barbara Zajc was hired with RCMI funds during the current grant period in the area of Bioorganic Chemistry. She studies DNA-carcinogen conjugates following the incorporation of fluorine as a modulator of biological activity and monitors structural changes that result form these modifications. Our central facility now has two Molecular Dynamics phosphoimagers and a Molecular Dynamics Laser Densitometer and these are of general utility to everyone in RCMI. Accomplishments of Area I Faculty and Research Highlights A majority of the Area I faculty (Balogh-Nair, Ghose, Gunner, Lazaridis, Schulz, Tasayco, Zajc) are well funded by external grants. Dr. Schulz was invited to write a book chapter entitled ¿Oxidation of Fatty Acids in Eukaryotes¿ and he serves on the Medical Biochemistry Study Section at the NIH. Dr. Gunner was honored with a Presidential Early Career Award for Scientists and Engineers (PECASE) with a $0.5 million grant. Summary of Faculty Research Dr. Balogh-Nair (Chemistry) is engaged in the synthesis of dendrimers with enhanced activities towards M-tropic HIV-1 viral strains. In contrast to traditional polymers, dendrimers are unique core-shell structures possessing three basic architectural components: (a) a core, (b) an interior of shells (generation) consisting of repetitive branch cell units, and (c) terminal functional groups, I.E., the outer shell or periphery. Dr. Ghose focuses on the development and implementation of novel NMR techniques to probe the structure and dynamics of biomolecules. He is also interested in deciphering the structure-function relationships in key enzymes involved in the Src-signaling pathway. He has recently published a paper in the J. of Biomolecular NMR on novel NMR methods that probe slow correlated motions in proteins. Dr. Gunner (Biophysics), an RCMI hire, is working to (a) develop tools to analyze and compare the energies of charged groups in proteins, (b) analyze the function of electron and proton where side chain or substrate ionization states are important for function, and (c) survey the protein structural data bank to identify motifs that stabilize buried charges. Dr. Lazaridis made a big step forward during the past year towards modeling of membrane proteins by developing an effective energy function for proteins in lipid bilayers as an extension of his EEF1 aqueous solution energy function. Dr. Schulz (Biochemistry) has a major goal to provide a detailed understanding of the reactions and auxiliary enzymes that are specifically required for the b-oxidation of unsaturated and hydroxy fatty acids. Dr. Tasayco (Biochemistry), an RCMI hire, produced a pioneering publication in Biochemistry using differential scanning calorimetry to recognize regions with residual structure in a family of complementary disordered protein fragments. She is currently studying the residual structure in the unfolded state of proteins by NMR spectroscopy to provide benchmarks for the prediction of protein energetics. Dr. Zajc studies the structure-activity relationships (SAR) in the area of chemical carcinogenesis. Specifically, she is addressing the SAR studies of DNA-carcinogen conjugates via site-specific incorporation of fluorine as a modulator of biological activity, to evaluate structural changes that occur upon such modifications.