在蛋白质序列同质学的黄昏区:蛋白质语言模型学习蛋白质结构吗?
Anowarul Kabir1, Asher Moldwin1, Yana Bromberg2
1Department of Computer Science, George Mason University, Fairfax, VA 22030, United States.
Bioinformatics advances
|August 26, 2024
概括
蛋白质语言模型隐式地学习结构,但在低序列身份的情况下,他们难以与远程同质性预测作斗争. 需要进一步的研究,以提高他们对蛋白质结构的理解,以实现这些具有挑战性的预测.
科学领域:
- 计算生物学 计算生物学
- 生物信息学是一种生物信息学.
- 机器学习在生物学中的应用
背景情况:
- 基于变压器的蛋白质语言模型 (PLM) 在各种蛋白质预测任务中表现有前途.
- 仅在序列上训练的PLM似乎隐含地捕获结构信息.
- 对于PLM在多大程度上编码蛋白质结构信息仍然是一个悬而未决的问题.
研究的目的:
- 调查PLM学习的序列表示是否编码结构信息.
- 量化PLM中编码的结构信息的范围.
- 评估PLM在远程同类预测方面的表现,特别是在低序列身份的黄昏区域.
主要方法:
- 在远程同质性预测任务上评估了PLM.
- 在逐渐较低的序列标识上测试了性能,以探测暮色区.
- 评估了各种PLM,参数范围从数百万到数十亿在零射击设置.
主要成果:
- 基于变压器的PLM超越了传统的序列对齐方法.
- 在非常低序列身份的黄昏区域中,PLM表现出显著的性能下降.
- 目前的PLM还没有足够了解蛋白质结构,以可靠地预测弱序信号的远程同质性.
结论:
- PLM显示出潜力,但需要进一步开发以进行强大的远程同质预测.
- 这项研究强调了需要在PLM中改进序列和结构丰富的表示.
- 公共可用的代码,数据和模型促进了该领域的未来研究.
相关概念视频
Protein Organization
6.3K
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....
6.3K
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 Families
15.3K
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...
15.3K
Protein and Protein Structure
79.2K
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...
A protein's shape is critical to its function. For example, an enzyme...
79.2K
Protein Folding
117.7K
Overview
117.7K
Protein and Protein Structures
10.4K
10.4K


