An Algorithm for Protein Switch Design

蛋白质开关设计算法

• 批准号: 7281956
• 负责人: XAVIER AMBROGGIO
• 金额: $ 2.44万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-01 至 2008-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7281956
• 关键词: Adopted; Algorithms; Amino Acid Sequence; Amino Acid Substitution; Amino Acids; Arizona; Behavior; Biotechnology; Cellular biology; Collaborations; Collection; Compatible; Condition; Depth; Development; Family; Fellowship; Homo; Individual; Laboratories; Ligand Binding; Mediating; Medical; Medicine; Metals; Methods; Molecular; Molecular Machines; Names; Nature; Numbers; Oxidation-Reduction; Peptide Sequence Determination; Procedures; Proteins; Public Health; Side; Simulate; Structure; Testing; Universities; Validation; Viral; Zinc; Zinc Fingers; design; disease-causing mutation; environmental change; improved; novel; oxidation; protein folding; protein structure; response; transcription factor

PTION (provided by applicant): Computational protein design has advanced rapidly from initial studies aimed at increasing the stability of naturally occurring proteins to the recent complete design of a novel protein fold. Our ability to create amino acid sequences compatible with given structures is evidence of the depth of our understanding of the underlying physical determinants of protein stability. Yet, the functions of many proteins depend on the ability of their primary sequences to adopt differing structures in response to changing environmental conditions. To understand this subtle aspect of protein folding, current design algorithms will be improved to optimize the design of a sequence compatible with multiple structures dependent upon environmental context. A select group of proteins will be redesigned to switch structures and this behavior will be experimentally validated. In addition to broadening our understanding of disease causing mutations that interfere with the propensity of cellular proteins for their target structures, these new methods will expand our ability to rationally design molecular switches for medical applications.

PTION（由申请人提供）：计算蛋白质设计从最初旨在提高天然蛋白质稳定性的研究发展到最近完整设计的新型蛋白质折叠。我们创造与给定结构相容的氨基酸序列的能力证明了我们对蛋白质稳定性的潜在物理决定因素的深入理解。然而，许多蛋白质的功能取决于其一级序列响应不断变化的环境条件而采用不同结构的能力。为了理解蛋白质折叠的这一微妙方面，将改进当前的设计算法，以优化与取决于环境背景的多种结构兼容的序列的设计。一组选定的蛋白质将被重新设计以转换结构，并且这种行为将得到实验验证。除了扩大我们对干扰细胞蛋白质对其目标结构的倾向的疾病突变的理解之外，这些新方法还将扩大我们合理设计用于医疗应用的分子开关的能力。