COMPUTATIONAL NEUROPEPTIDE DESIGN AND RECEPTOR MATCHING

计算神经肽设计和受体匹配

• 批准号: 6185861
• 负责人: ARNOLD Joseph MANDELL
• 金额: $ 37.5万
• 依托单位: CIELO INSTITUTE, INC.
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-07-01 至 2002-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6185861
• 关键词: artificial intelligence; bioimaging /biomedical imaging; cholecystokinin; computer assisted sequence analysis; computer program /software; computer simulation; computer system design /evaluation; dopamine receptor; neuropeptide receptor; neuropeptides; protein engineering; protein sequence; receptor expression

DESCRIPTION: (Verbatim from the Applicant's Abstract) Proprietary computational and graphical techniques combine elements of eigenvalue and wavelet decompositions, maximum entropy power spectra and "ergodic" measure theoretical methods (useful for the analyses of irregular series in hydrodynamic turbulence and plasma physics) with thermodynamic transformation of the amino acids in broad classes of globular and membrane proteins, including G-protein and tyrosine kinase coupled receptors, transporters, pores and channels. In the proposed work, these methods will be used to: 1) Create a referential, graphical atlas of protein sequence transformations through which to characterize and categorize new nucleotide and protein sequences with weak or absent specific amino acid, database homology. The atlas will be used in commercial consultation with investigators confronted with this problem; 2) From only a receptor's primary sequence, generate completely new libraries of membrane protein-targeted, regulatory peptides; and 3) Survey these algorithmically designed new peptides for sequence dependent potentiating or inhibiting influences on natural ligand-induced physiological activity, as demonstrated by microphysiometric assays of native or receptor cDNA transfected cell systems. The resulting physiologically active, patentable peptides will be used in commercial collaboration with research laboratories searching for probes of membrane protein allosteric sites and with drug companies developing respiratory delivery systems for peptide drugs. PROPOSED COMMERCIAL APPLICATION: We are using novel algorithmic techniques to design novel peptides that modulate the function of receptors and other proteins. There are two commercial applications of our work: (1) The licensing of our patented (in process) methods of peptide drug design to pharmaceutical firms; (2) The licensing of our new protein-targeted peptides for use in basic research and clinical testing and potential clinical use by pharmaceutical firms.

描述：（逐字摘自申请人摘要）专有的计算和图形技术将特征值和小波分解、最大熵功率谱和“遍历”测量理论方法（用于分析流体动力湍流和等离子体物理学中的不规则序列）与热力学元素相结合氨基酸在多种球状和膜蛋白中的转化，包括 G 蛋白和酪氨酸激酶偶联受体、转运蛋白、孔和通道。在拟议的工作中，这些方法将用于：1）创建蛋白质序列转换的参考图形图集，通过该图集对具有弱或不存在特定氨基酸、数据库同源性的新核苷酸和蛋白质序列进行表征和分类。该图集将用于与面临此问题的调查人员进行商业咨询； 2) 仅从受体的一级序列生成全新的膜蛋白靶向调节肽文库； 3) 调查这些算法设计的新肽对天然配体诱导的生理活性的序列依赖性增强或抑制影响，如天然或受体 cDNA 转染细胞系统的微生理测定所证明的。由此产生的具有生理活性、可申请专利的肽将用于与寻找膜蛋白变构位点探针的研究实验室以及开发肽药物呼吸输送系统的制药公司进行商业合作。拟议的商业应用：我们正在使用新颖的算法技术来设计调节受体和其他蛋白质功能的新颖肽。 我们的工作有两个商业应用：（1）将我们的肽药物设计专利（正在进行中）方法许可给制药公司； (2) 许可我们的新型蛋白质靶向肽用于基础研究和临床测试以及制药公司的潜在临床用途。