AREA I BIOMOLECULAR STRUCTURE & FUNCTION: AIDS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 第一领域的主要目标是阐明生物蛋白质的结构和功能， 分子，目的是理解和解释它们在发育中的功能 和细胞事件中。 五年续约的一项重大新举措是招募一名新的 X射线衍射蛋白质结构测定领域的教员 并提供启动资金来装备这个设施。 我们请求租用一台X光透视机 晶体学家的动机是需要补充和加强正在进行的 通过NMR进行的结构工作。 我们还做了X射线晶体分析 这是由诺华捐赠的设备，并通过学院的资金建立， 新的途径生物信息学和生物技术中心在CCNY。 生物化学和结构生物学的最新发展使I区的成员能够 进一步扩大研究领域，进入大分子和高分子 组件. 为了提高生产力和竞争力，他们必须利用新的 技术，并转向增加使用核磁共振技术结合核磁共振 这些设施是纽约市结构生物学中心不可或缺的， 2002年12月16日在我们的校园开幕。 在雅阁与这一目标，我们增加了一个 核磁共振光谱学专家罗尼·高斯博士请到I区 此次招聘得到了 RCMI在我们的最后一次赠款续期。 他开展了一项令人兴奋的独立研究， 计划，并获得了校外资助。 他积极与所有成员互动， 我区和其他区的成员也一样。 我们的设备不断改进和更新。 在过去的一年里， 和一台600 MHz频谱仪交付并投入使用， 马歇尔克科学大楼 这些机器的成本由学院和 和RCMI。 这种新功能进一步扩展了质谱法的使用范围， 大而脆弱的分子，并使这种工具可用于生物学领域的研究人员， 以理工科为重 Barbara Zajc在本赠款期内被RCMI基金聘用， 生物有机化学 她研究DNA-致癌物结合物， 掺入氟作为生物活性的调节剂并监测结构 由这些修改引起的变化。 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磷光成像仪。 动态激光密度计和这些都是通用的RCMI的每个人。 第一领域教师的成就和研究亮点 大部分的第一区教师（巴洛格奈尔，戈塞，枪手，拉扎里茨，舒尔茨，塔萨科， Zajc）得到了外部赠款的良好资助。 舒尔茨博士被邀请写一本书的章节 题为“真核生物中脂肪酸的氧化”，他在医学 美国国立卫生研究院生物化学研究科。 冈纳博士被授予总统早期 科学家和工程师职业奖（PECASE），50万美元赠款。 教师研究总结 博士Balogh-Nair（化学）从事树枝状聚合物的合成， 对M嗜性HIV-1病毒株的活性。 与传统聚合物相比， 树枝状聚合物是独特的核-壳结构，具有三种基本的结构 组分：（a）核心，（B）由重复的分支组成的壳（代）的内部 细胞单位，和（c）末端官能团，即，外壳或外围。 博士Ghose专注于新型NMR技术的开发和实施 来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。 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 探测蛋白质中缓慢的相关运动。 博士Gunner（生物物理学）是RCMI的一名雇员，他正在致力于（a）开发分析和 比较蛋白质中带电基团的能量，（B）分析电子的作用 和质子，其中侧链或底物电离状态对功能很重要，和 (c)调查蛋白质结构数据库，以确定稳定掩埋电荷的基序。 博士在过去的一年里，拉扎里恩在建模方面迈出了一大步。 通过开发脂质双层中蛋白质的有效能量函数， 作为他的EEF 1水溶液能量函数的扩展。 博士Schulz（生物化学）的一个主要目标是提供一个详细的了解， 反应和辅助酶，特别是所需的B-氧化 不饱和和羟基脂肪酸。 博士Tasayco（生物化学）是RCMI的一名雇员， 生物化学使用差示扫描量热法识别具有残留的区域 互补无序蛋白质片段家族中的结构。 她目前正在 通过NMR光谱研究蛋白质未折叠状态下的残留结构， 为蛋白质能量学的预测提供基准。 博士Zajc研究化学领域的结构-活性关系（SAR） 致癌作用 具体来说，她正在解决DNA致癌物的SAR研究， 通过位点特异性掺入氟作为生物活性调节剂的缀合物， 以评估在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.