死亡消除定理及其在蛋白质侧链定位中的应用
J Desmet1, M De Maeyer, B Hazes
1Interdisciplinary Research Center, KU Leuven Campus Kortrijk, B8500 Kortrijk, Belgium.
Nature
|April 15, 2011
概括
预测蛋白质结构是很困难的,因为庞大的形状空间. 这项研究引入了死结消除定理,以有效地识别不可用的侧链构造,使大蛋白质集合的全球最小能量确定成为可能.
科学领域:
- 计算生物学 计算生物学
- 结构生物学 结构生物学
- 蛋白质科学 蛋白质科学
背景情况:
- 预测蛋白质的三级结构仍然是一个重要的计算挑战.
- 现有的侧链建模方法,如旋转器分组,在大型系统中面临局限性.
- 详尽的搜索仅限于小蛋白质单元,需要更大的结构的替代策略.
研究的目的:
- 为高效的蛋白质侧链建模提出一个新的定理.
- 为了解决确定蛋白质的全球最小能量构成的计算复杂性.
- 为了能够准确地预测较大的蛋白质集合的三级结构.
主要方法:
- 介绍了"死胡同消除"定理.
- 开发一种条件,以识别和排除非最佳旋转器.
- 该定理的应用来控制侧链形态搜索中的组合复杂性.
主要成果:
- 死亡消除定理有效地削减了构造性搜索空间.
- 在rotamer组合问题中的计算爆炸得到了显著的控制.
- 该方法允许确定广泛的侧链集合的全球最小能量构造.
结论:
- 死亡消除定理为蛋白质结构预测提供了一个有效的计算策略.
- 这种方法克服了以前大规模侧链建模方法的局限性.
- 对于较大的蛋白质系统来说,现在可以准确地确定全球最小能量构造.
相关概念视频
Conserved Binding Sites
Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally analyses the...
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally analyses the...
Conserved Binding Sites
Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally analyses the...
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally analyses the...
Protein Folding
Overview
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...
Conservation of Protein Domains Over Different Proteins
Protein domains are small structurally independent units that are part of a single amino acid chain. Although these domains are often structurally independent, they may rely on synergistic effects to perform their functions as part of a larger protein. Protein domains may be conserved within the same organism, as well as across different organisms.
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to form...
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to form...
Termination of Translation
The large ribosomal subunit has several important structures essential to translation. These include the peptidyl transferase center (PTC) - which is the site where the peptide bond is formed - and a large, internal, water-filled tube through which the nascent polypeptide moves. This latter structure is called the Peptide Exit Tunnel, and it begins at the PTC and spans the body of the large ribosomal subunit. During translation, as the nascent polypeptide chain is synthesized, it passes through...


