COMPUTATIONAL NEUROPEPTIDE DESIGN AND RECEPTOR MATCHING

计算神经肽设计和受体匹配

基本信息

批准号：
6021666
负责人：
ARNOLD Joseph MANDELL
金额：
$ 2.25万
依托单位：
CIELO INSTITUTE, INC.
依托单位国家：
美国
项目类别：
财政年份：
1998
资助国家：
美国
起止时间：
1998-03-01 至 1999-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6021666
关键词：
artificial intelligence cell line cholecystokinin computer assisted sequence analysis computer program /software computer system design /evaluation dopamine receptor hydropathy neuropeptide receptor neuropeptides neurotensin protein engineering protein sequence receptor expression

项目摘要

The development of a prototype software package, the Gen-Pep Algorithm, an entirely new, receptor sequence, hydrophobic free energy eigenfunction-based proprietary system for short peptide design, will be completed. Its feasibility with respect to a yield of new peptides which elicit target receptor-mediated biological activation in receptor cDNA transfected cell lines will be tested using Cytosensor Microphysiometry. Gen-Pep exploits a sequence of linear transformations of the hydrophobic free energies of the amino acid sequences of peptide and their receptors and includes eigenvalue decomposition and complex pole spectral and wavelet transformation and a constructive step using the leading eigenvectors. Given a peptide receptor sequence, this system generates a family of candidate peptides to interact with it. As exemplars, short peptide analogues of neurotensin and cholecystokinin will be designed and tested for their recently demonstrated direct action on the D2 dopamine receptor and the dopamine transporter proteins respectively. New short peptide analogues of (longer peptide) epidemoid growth factor, transforming growth factor and fibrobast growth factor will be designed and tested similarly. Licensing and support of Gen-Pep including a superfamily hydrophobic free energy eigenfunction library, contract new peptide development for biotechnology, companies and new peptide-drug development constitute the three commercial goals of the enterprise. PROPOSED COMMERCIAL APPLICATION 1) Licensing Gen-Pep software, support and eigenfunction library for an annual fee to biotechnology and pharmaceutical research concerns. 2) Contracting with similar entities for Cielo Institute, Inc. to generate and preliminarily test promising candidate, short peptides designed for specific purposes. 3) Developing and testing new peptide ligands for patenting by Cielo Institute, Inc.

开发原型软件包，Gen-PEP算法，一个全新的受体序列，疏水自由能基于特征函数的简短肽设计专有系统，将完成。它关于新肽产量的可行性哪些引起靶基受体介导的受体生物激活 cDNA转染的细胞系将使用细胞传感器进行测试显微生理测量法。 Gen-Pep利用一系列线性氨基酸疏水自由能的转化肽及其受体的序列，包括特征值分解和复杂的杆光谱和小波转化以及使用领先的特征向量的建设性步骤。给定肽受体序列，该系统生成一系列候选肽与之互动。作为示例，短的肽类似物神经辛素和胆囊动蛋白将经过设计和测试最近在D2多巴胺受体和多巴胺转运蛋白分别。新的短肽类似物（较长的肽）附子生长因子，转化生长因子和纤维测试生长因子将被类似地设计和测试。 Gen-Pep的许可和支持，包括超家族疏水性自由能本本函数库，合同的新肽开发生物技术，公司和新肽 - 药物发展构成企业的三个商业目标。拟议的商业应用 1）许可GEN-PEP软件，支持和本本函数库生物技术和药品研究的年费。 2）与Cielo Institute，Inc。的类似实体签约以生成并初步测试有希望的候选人，设计的短肽具体目的。 3）开发和测试新的肽配体 Cielo Institute，Inc。专利