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：（（逐字化申请人的摘要）专有计算和图形技术结合了特征值和小波分解的要素，最大的熵功率谱以及“厄尔贡”测量方法（用于无限制序列的分析）在水流动力学和质谱型中的不规则串联分析与热力学转化中的分析，并在热力学类别中进行热力学转化。蛋白质，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）创建一个蛋白质序列转化的参照图形图图图集，通过该图表和分类具有弱或缺乏特定氨基酸的新核苷酸和蛋白质序列，数据库同源性。该地图集将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中产生全新的膜蛋白靶向调节肽的文库； 3）调查这些算法设计的新肽，用于依赖于天然配体诱导的生理活性的序列增强或抑制影响，如天然或受体cDNA转染的细胞系统的微生物分析测定所示。由此产生的生理活性，可专利的肽将用于与搜索膜蛋白质变构探针的研究实验室的商业合作，并与制药公司开发用于肽药物的呼吸道输送系统。拟议的商业应用：我们正在使用新型算法技术来设计调节受体和其他蛋白质功能的新型肽。 我们的工作有两个商业应用：（1）我们在制药公司的肽药物设计专利（过程中）的许可； （2）我们将新的蛋白质靶向肽的许可用于基础研究和临床测试以及制药公司潜在的临床使用。