在家庭中保持它:使用蛋白质家族模板来拯救低可信度的AlphaFold2模型
Francesco Costa1, Matthias Blum1, Alex Bateman1
1European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Hinxton CB10 1SD, United Kingdom.
Bioinformatics advances
|December 11, 2024
概括
改善蛋白质结构预测是关键. 我们的研究表明,低置信度的AlphaFold2模型可以使用高置信度的家族模板来挽救,提高准确性和速度.
科学领域:
- 计算生物学是一种计算生物学.
- 结构生物信息学 结构生物信息学
- 蛋白质结构预测 蛋白质结构预测
背景情况:
- 像AlphaFold2这样的高可信度蛋白质结构预测模型广泛可用,超过2亿个模型是公开可用的.
- 在蛋白质家族内,预测信心 (plDDT得分) 存在显著的变化.
- 使用高信心家庭成员作为模板来改善低信心预测的潜力仍未得到充分探索.
研究的目的:
- 为了调查蛋白质家族中较低的plDDT预测是否可以通过在AlphaFold2.2.中使用来自同一家族的较高的plDDT模板来增强.
- 探索改善蛋白质结构预测准确性和信心的替代策略.
主要方法:
- 使用高plDDT蛋白质结构模型作为相同蛋白质家族内的较低plDDT模型的模板.
- 将标准AlphaFold2预测和模板增强预测之间的预测信心 (plDDT) 和结构质量指标进行比较.
- 评估关闭多重序列对齐 (MSA) 选项的影响,并仅依赖模板.
- 在NextFlow中实现一个管道,用于可复制的分析,可在GitHub上找到.
主要成果:
- 大约三分之一的低信心预测 (低plDDT) 被成功改进到合理的信心水平.
- 在一些情况下,禁用MSA选项和使用高质量的模板导致了更高的plDDT分数.
- 最优的策略涉及生成带有和没有MSA信息的预测,选择具有最高平均plDDT的模型.
- 使用高plDDT模型作为模板加速了ColabFold中的AlphaFold2预测.
- 根据两个指标,改进的模型不仅显示了plDDT的增加,而且显示了结构质量的可能改善.
结论:
- 基于模板的增强提供了一种可行的方法来拯救和改进低可信度蛋白质结构预测.
- 战略性使用模板,可能与MSA信息相结合,可以优化预测准确性和效率.
- 开发的管道为研究人员提供了一个实用的工具,以提高蛋白质结构模型的质量.
相关概念视频
Protein Families
15.2K
Protein families are groups of homologous proteins; that is, they have similarities in amino acid sequences and three-dimensional structures. Protein families usually occur because of gene duplication, where an additional copy of a gene is inserted into the genome of an organism. Mutations that change the amino acids but still allow the protein to be properly synthesized, will lead to new protein family members. If these new proteins contain similar amino acids in key...
15.2K
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
Protein Folding
7.8K
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...
7.8K
Protein Organization
6.2K
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....
6.2K
Protein Folding Quality Check in the RER
3.7K
ER is the primary site for the maturation and folding of soluble and transmembrane secretory proteins. The calnexin cycle is a specific chaperone system that folds and assesses the confirmation of N-glycosylated proteins before they can exit the ER lumen. The primary players of this quality check pipeline are the lectins, ER-resident chaperones, and a glucosyl transferase enzyme. In case the calnexin system in the lumen fails to salvage a misfolded protein, it is transported to the cytoplasm...
3.7K
Conservation of Protein Domains
3.1K
3.1K


