一个精心策划的Rotamer图书馆,用于常见的蛋白质翻译后修改
Oufan Zhang1, Shubhankar A Naik2, Zi Hao Liu3,4
1Kenneth S. Pitzer Center for Theoretical Chemistry, University of California, Berkeley, Berkeley, California 94720, USA.
ArXiv
|May 20, 2024
概括
这项研究提出了新的侧链旋转子库,用于蛋白质的翻译后修饰 (PTM). 这些库增强了对折叠蛋白和内在无序蛋白 (IDP) 的蛋白质结构预测.
科学领域:
- 结构生物学 结构生物学
- 计算生物学 计算生物学
- 生物化学 生物化学
背景情况:
- 侧链旋转子库对于蛋白质结构的确定和内在无序蛋白质 (IDP) 的建模至关重要.
- 翻译后修改 (PTMs) 显著调节蛋白质功能,但通常在现有的旋转分子库中没有充分表现.
- 准确的PTM建模对于了解蛋白质功能和动态至关重要.
研究的目的:
- 为常见的PTMs创建全面的侧链旋转器库.
- 提高含有PTMs的实验蛋白质结构的预测准确度.
- 为了证明这些库在建模折叠蛋白和IDP中的实用性.
主要方法:
- 从RCSB PDB数据库中对化,甲基化和乙化氨基酸进行了一组侧链旋转器.
- 与折叠蛋白质的实验结构相对应的验证的旋转分子库.
- 使用蒙特卡罗侧链 (MCSCE) 和 IDPConformerGenerator 生成的蛋白质组合,包含 PTM 库.
主要成果:
- 开发了用于常见PTM的新型旋转分子库,在预测含有PTM的蛋白质结构方面超过了SIDEpro和Rosetta等现有方法.
- 成功地应用了PTM库来生成使用MCSCE的折叠蛋白质合集.
- 集成的PTM库与IDPConformerGenerator,用于增强对具有内在无序区域的蛋白质的建模.
结论:
- 新的PTM旋转体库显著提高了对修饰蛋白质的蛋白质结构预测的准确性.
- 这些库对于折叠蛋白质结构的确定和对内在无序蛋白质的结构分析都是有价值的工具.
- 这项工作为对受PTMs影响的蛋白质功能的更准确的计算研究提供了基础.
相关概念视频
Covalently Linked Protein Regulators
6.8K
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....
These groups modify specific amino acids in a protein....
6.8K
Protein Modifications in the RER
5.1K
Modification of secretory and transmembrane proteins entering the rough ER begins in the ER lumen. These modifications aid in protein folding and stabilize the acquired tertiary structure. Protein modifications in the rough ER co-occur at different stages of protein folding.
Broadly, these modifications can be categorized into four main categories — glycosylation, formation of disulfide bonds, assembly of protein subunits, and specific proteolytic cleavages like removal of signal...
Broadly, these modifications can be categorized into four main categories — glycosylation, formation of disulfide bonds, assembly of protein subunits, and specific proteolytic cleavages like removal of signal...
5.1K
Directing Proteins to the Rough Endoplasmic Reticulum
7.2K
The organelle-specific signaling sequences direct proteins synthesized in the cytosol to their final destination like ER, mitochondria, peroxisomes, etc. Some of the proteins directed to ER are then trafficked via vesicles to other organelles within the cell or the extracellular environment through the Golgi complex. For example, the rough ER synthesizes soluble proteins for transportation to the lysosomes or secretion out of the cell. It can also synthesize transmembrane proteins that can...
7.2K
Conservation of Protein Domains Over Different Proteins
10.8K
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...
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to...
10.8K
Ligand Binding and Linkage
4.8K
Allosteric proteins have more than one ligand binding site; the binding of a ligand to any of these sites influences the binding of ligands to the other sites. When a protein is allosteric, its binding sites are called coupled or linked. In the case of enzymes, the site that binds to the substrate is known as the active site and the other site is known as the regulatory site. When a ligand binds to the regulatory site, this leads to conformational changes in the protein that can influence...
4.8K
Transfer RNA Synthesis
11.9K
One of the unique features of tRNA is the presence of modified bases. In some tRNAs, modified bases account for nearly 20% of the total bases in the molecule. Altogether, these unusual bases protect the tRNA from enzymatic degradation by RNases.
Each of these chemical modifications is carried by a specific enzyme, post-transcription. All of these enzymes have unique base and site-specificity. Methylation, the most common chemical modification, is carried by at least nine different enzymes, with...
Each of these chemical modifications is carried by a specific enzyme, post-transcription. All of these enzymes have unique base and site-specificity. Methylation, the most common chemical modification, is carried by at least nine different enzymes, with...
11.9K


