通过碳化合物基质稳定酸中的α螺旋结构的全原子模型
Peter S Kutchukian1, Jae Shick Yang, Gregory L Verdine
1Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, Massachusetts 02138, USA.
Journal of the American Chemical Society
|April 2, 2009
概括
碳化合物接增强了的α螺旋稳定性,改善了药物的特性. 模拟显示,主稳定诱状态,这对于理解药物设计中的螺旋稳定机制至关重要.
科学领域:
- 生物化学 生物化学
- 计算化学计算化学
- 药物发现 药物发现 药物发现
背景情况:
- 与碳化合物链接器的接增强了阿尔法螺旋倾向.
- 拼接提供了更好的药物特性,包括稳定性和透性.
- 它们显示了向细胞内蛋白质与蛋白质相互作用的潜力.
研究的目的:
- 为了理解由碳化合物主体控制螺旋稳定力的力量.
- 为了研究主食合并的上下文依赖性.
- 为了比较不同主料长度 (i,i+4 vs. i,i+7) 的效果.
主要方法:
- 全原子的蒙特卡洛折叠模拟.
- 将未经修改的与各种压缩版 (i,i+4 和 i,i+7) 的比较.
- 在RNase A和BID BH3衍生的上进行的模拟.
主要成果:
- 模拟结果与实验螺旋倾向量上一致.
- 发现碳化合物主食可以稳定准稳定的诱形状.
- 删除这些诱状态显著影响了螺旋体的整体稳定性.
结论:
- 碳化合物主食提供了稳定α螺旋的有希望的策略.
- 了解诱状态稳定是优化聚合设计的关键.
- 这项工作提供了对固定的稳定机制的物理洞察.
相关概念视频
Protein Organization
Overview
Protein Organization
Proteins are polymers of amino acid residues. They are versatile and responsible for different cellular functions, including DNA replication, molecular transport, catalysis, and structural support. Proteins have a hierarchical structure comprising at least three levels of organization: primary, secondary, and tertiary structure. Some large proteins have a quaternary structure where individual protein subunits are linked together.
The primary structure of a protein is its amino acid sequence.
The primary structure of a protein is its amino acid sequence.
Protein Folding
Proteins are chains of amino acids linked together by peptide bonds. Upon synthesis, a protein folds into a three-dimensional conformation, critical to its biological function. Interactions between its constituent amino acids guide protein folding, and hence the protein structure is primarily dependent on its amino acid sequence.
Protein Structure Is Critical to Its Biological Function
Proteins perform a wide range of biological functions such as catalyzing chemical reactions, providing...
Protein Structure Is Critical to Its Biological Function
Proteins perform a wide range of biological functions such as catalyzing chemical reactions, providing...
Protein Folding
Overview
Protein and Protein Structure
Proteins are one of the most abundant organic molecules in living systems and have the most diverse range of functions of all macromolecules. Proteins may be structural, regulatory, contractile, or protective. They may serve in transport, storage, or membranes; or they may be toxins or enzymes. Their structures, like their functions, vary greatly. They are all, however, amino acid polymers arranged in a linear sequence.
A protein's shape is critical to its function. For example, an enzyme can...
A protein's shape is critical to its function. For example, an enzyme can...
Peptide Bonds
A peptide bond covalently attaches amino acids through a dehydration reaction. One amino acid's carboxyl group and another amino acid's amino group combine, releasing a water molecule. The resulting bond is the peptide bond. The products that such linkages form are peptides. As more amino acids join this growing chain, the resulting chain is a polypeptide. Each polypeptide has a free amino group at one end. This end has the N-terminal, or the amino-terminal, and the other end has a free...


