药物可替代蛋白的全面研究:从PSSM到预训练的语言模型
1College of Information Technology, Shanghai Ocean University, Shanghai 201306, China.
International journal of molecular sciences
|April 27, 2024
概括
这项研究引入了一种快速而准确的计算方法,用于使用先进的蛋白质语言模型 (PLM) 识别可用药物的蛋白质. 这种新的方法通过优于传统方法显著提高了药物发现效率.
科学领域:
- 计算生物学是一种计算生物学.
- 药物发现 药物发现
- 生物信息学是一种生物信息学.
背景情况:
- 识别可用药的蛋白质对于具有成本效益的药物发现至关重要.
- 传统的实验方法是缓慢的,昂贵的,劳动密集型的大规模查.
- 计算方法为预测蛋白质可用性提供了有效的替代方案.
研究的目的:
- 开发一个快速而精确的计算分类器来识别可用药的蛋白质.
- 对传统特征进行蛋白质语言模型 (PLM) 嵌入的性能评估.
- 探索大型语言模型 (LLM) 的应用,用于药物可用蛋白质的识别.
主要方法:
- 采用蛋白质语言模型 (PLM) 与微调的进化规模建模2 (ESM-2) 嵌入式进行分类.
- 将ESM-2嵌入的预测性能与位置特定评分矩阵 (PSSM) 功能进行了比较.
- 开发并测试了一种基于修改后的生成预训练变压器2 (GPT-2) 的端到端模型.
- 使用基准数据集和Pharos数据集验证了模型.
主要成果:
- 在使用ESM-2嵌入物识别可用药物的蛋白质方面获得了95.11%的准确性.
- 与PSSM特征相比,ESM-2嵌入显示出更高的准确性和效率.
- 这项研究代表了GPT-2 LLM首次用于药物可用蛋白质识别的部署.
结论:
- 蛋白质语言模型,特别是ESM-2嵌入式,提供了一个非常准确和有效的方法来识别可用药的蛋白质.
- 开发的计算模型可以显著加速药物发现的早期阶段.
- 像GPT-2这样的LLM显示了促进蛋白质功能预测和药物标识的前景.
更多相关视频
06:50Author Spotlight: A Computational Approach to Decipher Amino Acid Preferences in Multispecific Protein-Protein Interactions
Published on: January 26, 2024
1.8K
08:31Biosensor-based High Throughput Biopanning and Bioinformatics Analysis Strategy for the Global Validation of Drug-protein Interactions
Published on: December 1, 2020
5.0K
相关概念视频
Protein-protein Interfaces
12.5K
Many proteins form complexes to carry out their functions, making protein-protein interactions (PPIs) essential for an organism's survival. Most PPIs are stabilized by numerous weak noncovalent chemical forces. The physical shape of the interfaces determines the way two proteins interact. Many globular proteins have closely-matching shapes on their surfaces, which form a large number of weak bonds. Additionally, many PPIs occur between two helices or between a surface cleft and a...
12.5K
Ligand Binding Sites
12.8K
Proteins are dynamic macromolecules that carry out a wide variety of essential processes; however, the activities of most proteins depend on their interactions with other molecules or ions, known as ligands.
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
12.8K
Protein Networks
3.9K
An organism can have thousands of different proteins, and these proteins must cooperate to ensure the health of an organism. Proteins bind to other proteins and form complexes to carry out their functions. Many proteins interact with multiple other proteins creating a complex network of protein interactions.
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
3.9K
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-Drug Binding: Determination Methods
168
Determining protein-drug binding can be achieved through indirect and direct methods, each providing valuable insights into the interaction between proteins and drugs.
Indirect methods involve isolating the bound drug from its free form in biological samples such as blood, serum, or plasma. These techniques aim to measure the percentage of drugs bound to proteins. Equilibrium dialysis is a commonly used method where the free drug concentration at equilibrium is measured by separating the bound...
Indirect methods involve isolating the bound drug from its free form in biological samples such as blood, serum, or plasma. These techniques aim to measure the percentage of drugs bound to proteins. Equilibrium dialysis is a commonly used method where the free drug concentration at equilibrium is measured by separating the bound...
168
Drug Discovery: Overview
7.8K
Drug discovery is a multifaceted process involving extensive screening, testing, and optimization of lead compounds to identify potential new drugs for therapeutic use. It combines several approaches, including screening large numbers of natural products, chemical modification of known active molecules, identification of new drug targets, and rational design based on biological mechanisms and drug-receptor structure. These approaches are carried out in both academic research laboratories and...
7.8K
