AREA I BIOMOLECULAR STRUCTURE & FUNCTION: AIDS

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。 第一个主要领域的目标是阐明生物的结构和功能。 分子，目的是了解和解释它们在发育中的功能 在细胞活动中。续签五年的一项重大新举措是招募一名新的 确定蛋白质结构的X射线衍射领域的教员 并提供启动资金来装备这个设施。我们租用X光片的要求 结晶学家的动机是需要补充和加强正在进行的 由核磁共振进行的结构工作。我们还获得了X射线结晶学 设备由诺华公司捐赠，并于#年通过学院的资金建立 CCNY的新路径生物信息学和生物技术中心。 生物化学和结构生物学的最新发展使第一区的成员能够 进一步将研究领域拓展到大分子和大分子 装配。为了提高生产力和竞争力，他们必须利用新的 技术，并转向更多地使用核磁共振技术与核磁共振 作为纽约市结构生物学中心不可或缺的设施，正式 2002年12月16日在我校开学。为了实现这一目标，我们增加了一个 核磁共振波谱专家Ronnie Ghose博士到一区。 RCMI在我们最后一次的拨款续期中。他开展了一项令人振奋的独立研究 计划，并已获得外部资金。他积极地与所有成员互动 第一区和其他区的成员也是如此。 我们的设备在不断改进和更新。在过去的一年中，有1500人 一台600兆赫光谱仪已交付并在#年广场层投入使用 马沙克科学大楼。这些机器的费用由学院分摊 和RCMI。这一新功能将质谱学的使用进一步扩展到 大而脆弱的分子，并使这一工具可供研究人员在生物学 科学。 Barbara Zajc是在当前赠款期间用RCMI资金在以下地区受雇的 生物有机化学。她研究DNA-致癌物的偶联物 掺入氟作为生物活性的调节剂和监测结构 由于这些修改而产生的更改。 我们的中心设施现在有两台分子动力学磷光仪和一台分子 动力学激光密度计，这些都是通用的实用在RCMI的每个人。 第一区教师的成就和研究亮点 I区的大多数教员(Balogh-Nair，Ghose，Gunner，Lazaridis，Schulz，Tasayco， Zajc)由外部赠款提供充足的资金。舒尔茨博士应邀写了一本书的章节 题为《真核生物中的脂肪酸氧化》，他在 美国国立卫生研究院生物化学研究部。Gunner博士很早就被授予总统称号 科学家和工程师职业奖(PECASE)，拨款50万美元。 院系研究综述 Balogh-Nair博士(化学)从事树枝状大分子的合成 对M嗜性HIV-1病毒株的活性。与传统聚合物相比， 树枝状大分子是一种独特的核壳结构，具有三种基本结构 组件：(A)核心，(B)壳的内部(世代)，由重复的分支组成 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的核磁共振技术 探索生物大分子的结构和动力学。他对破译也很感兴趣 涉及Src信号通路的关键酶的结构与功能关系。 他最近在《生物分子核磁共振杂志》上发表了一篇关于新型核磁共振方法的论文。 该探测器减缓了蛋白质中的相关运动。 甘纳博士(生物物理学)是RCMI的一名雇员，他正在努力(A)开发工具来分析和 比较蛋白质中带电基团的能量，(B)分析电子的功能 以及侧链或底物电离态对功能重要的质子，以及 (C)调查蛋白质结构数据库，以确定稳定埋藏电荷的基序。 在过去的一年里，拉扎里迪斯博士在建立 通过为脂双层中的蛋白质开发有效的能量函数来实现膜蛋白质 作为他的EEF1水溶液能量函数的推广。 舒尔茨博士(生物化学)的一个主要目标是提供对 B-氧化所特别需要的反应和辅酶 不饱和脂肪酸和羟基脂肪酸。 Tasayco博士(生物化学)是RCMI的一名雇员，他在 用差示扫描量热法识别残留区的生物化学 一个互补的无序蛋白质片段家族中的结构。她目前 用核磁共振波谱研究蛋白质未折叠状态下的残基结构 为蛋白质能量学的预测提供基准。 Zajc博士研究化学领域的结构-活性关系(SAR) 致癌。具体地说，她是在谈DNA致癌物质的SAR研究 通过特定部位掺入氟作为生物活性调节剂的偶联物， 评估因此类修改而发生的结构变化。

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.