RNAmigos2:加快基于结构的RNA虚拟选与深度图形学习
Juan G Carvajal-Patiño1,2, Vincent Mallet3,4,5,6, David Becerra1,2
1School of Computer Science, McGill University, Montréal, QC, Canada.
Nature communications
|March 22, 2025
概括
我们开发了一种快速,数据驱动的深度学习方法,用于RNA药物标查. 这种基于结构的虚拟查 (VS) 方法显著加速了针对RNA标的潜在候选药物的识别.
科学领域:
- 生物化学 生化学
- 计算生物学 计算生物学
- 药物发现 药物发现 药物发现
背景情况:
- 核糖核酸 (RNA) 是潜在药物标的重要来源.
- 基于结构的虚拟查 (VS) 对于识别候选药物至关重要,但在RNA目标和大型化合物库方面面临挑战.
- 目前用于RNA VS的机器学习应用程序受到数据稀缺和不充分的验证的限制.
研究的目的:
- 开发和验证一个新的,数据驱动的VS管道,专门用于RNA目标.
- 为了克服传统分子对接的局限性,进行大规模的RNA查.
- 确定深度学习在基于结构的RNA药物发现中的有效性.
主要方法:
- 使用粗粒度3D建模和RNA特异性自我监督实现一个VS管道.
- 使用合成数据增强来增强模型训练.
- 采用深度学习模型,快速选化合物库与RNA结构.
主要成果:
- 与传统的对接方法相比,实现了1万倍的加快速度.
- 在多种不同的RNA结构中,始终将活性化合物排在2.8%的前列.
- 证明了对结合点变化的稳定性.
- 在一个体外微阵列 (20,000个化合物) 中成功选了新型RNA核糖转换器,平均丰富系数为2.93在1%.
结论:
- 开发的深度学习管道为基于结构的RNAVS提供了高效和准确的方法.
- 这项工作代表了对RNA VS.基于结构的深度学习的首次实验验证.
- 这种方法显著提升了发现向RNA分子的药物的潜力.
相关概念视频
RNA Structure
Overview
The basic structure of RNA consists of a five-carbon sugar and one of four nitrogenous bases. Although most RNA is single-stranded, it can form complex secondary and tertiary structures. Such structures play essential roles in the regulation of transcription and translation.
Different Types of RNA Have the Same Basic Structure
There are three main types of ribonucleic acid (RNA): messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). All three RNA types consist of a...
The basic structure of RNA consists of a five-carbon sugar and one of four nitrogenous bases. Although most RNA is single-stranded, it can form complex secondary and tertiary structures. Such structures play essential roles in the regulation of transcription and translation.
Different Types of RNA Have the Same Basic Structure
There are three main types of ribonucleic acid (RNA): messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). All three RNA types consist of a...
RNA Interference
RNA interference (RNAi) is a process in which a small non-coding RNA molecule blocks the post-transcriptional expression of a gene by binding to its messenger RNA (mRNA) and preventing the protein from being translated.
This process occurs naturally in cells, often through the activity of genomically-encoded microRNAs. Researchers can take advantage of this mechanism by introducing synthetic RNAs to deactivate specific genes for research or therapeutic purposes. For example, RNAi could be used...
This process occurs naturally in cells, often through the activity of genomically-encoded microRNAs. Researchers can take advantage of this mechanism by introducing synthetic RNAs to deactivate specific genes for research or therapeutic purposes. For example, RNAi could be used...
RNA Structure
Overview
The basic structure of RNA consists of a five-carbon sugar and one of four nitrogenous bases. Although most RNA is single-stranded, it can form complex secondary and tertiary structures. Such structures play essential roles in the regulation of transcription and translation.
Different Types of RNA Have the Same Basic Structure
There are three main types of ribonucleic acid (RNA): messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). All three RNA types consist of a...
The basic structure of RNA consists of a five-carbon sugar and one of four nitrogenous bases. Although most RNA is single-stranded, it can form complex secondary and tertiary structures. Such structures play essential roles in the regulation of transcription and translation.
Different Types of RNA Have the Same Basic Structure
There are three main types of ribonucleic acid (RNA): messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). All three RNA types consist of a...
RNA-seq
RNA sequencing, or RNA-Seq, is a high-throughput sequencing technology used to study the transcriptome of a cell. Transcriptomics helps to interpret the functional elements of a genome and identify the molecular constituents of an organism. Additionally, it also helps in understanding the development of an organism and the occurrence of diseases.
Before the discovery of RNA-seq, microarray-based methods and Sanger sequencing were used for transcriptome analysis. However, while microarray-based...
Before the discovery of RNA-seq, microarray-based methods and Sanger sequencing were used for transcriptome analysis. However, while microarray-based...
RNA Structure
The basic structure of RNA consists of a string of ribonucleotides attached by phosphodiester bonds. Although most RNA is single-stranded, it can form complex secondary and tertiary structures. Such structures play essential roles in the regulation of transcription and translation.
Different Types of RNA Have the Same Basic Structure
There are three main types of ribonucleic acid (RNA) involved in protein synthesis: messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). All three...
Different Types of RNA Have the Same Basic Structure
There are three main types of ribonucleic acid (RNA) involved in protein synthesis: messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). All three...
Nucleic Acid Structure
The pentose sugar in DNA is deoxyribose, while in RNA the pentose sugar is ribose. The difference between the sugars is the presence of the hydroxyl group on the ribose's second carbon and a hydrogen on the deoxyribose's second carbon. The phosphate residue attaches to the hydroxyl group of the 5′ carbon of one sugar and the hydroxyl group of the 3′ carbon of the sugar of the next nucleotide, which forms a 5′ to 3′ phosphodiester linkage.
DNA Structure
DNA has a double-helix structure. The...
DNA Structure
DNA has a double-helix structure. The...


