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Mutations01:39

Mutations

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Overview
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Mutations01:35

Mutations

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Mutations are changes in the sequence of DNA. These changes can occur spontaneously or they can be induced by exposure to environmental factors. Mutations can be characterized in a number of different ways: whether and how they alter the amino acid sequence of the protein, whether they occur over a small or large area of DNA, and whether they occur in somatic cells or germline cells.
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
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Language01:16

Language

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Language is a unique communication system that uses words and systematic rules to organize and transmit information. Unlike other forms of communication, which may involve postures, movements, odors, or vocalizations, language relies on symbols and grammar. This makes human communication distinct from that of other species, who also communicate but do not use language in the same way humans do.
Corballis and Suddendorf (2007) and Tomasello and Rakoczy (2003) highlight the role of language in...
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Viral Mutations00:36

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A mutation is a change in the sequence of bases of DNA or RNA in a genome. Some mutations occur during replication of the genome due to errors made by the polymerase enzymes that replicate DNA or RNA. Unlike DNA polymerase, RNA polymerase is prone to errors because it is not capable of “proofreading” its work. Viruses with RNA-based genomes, like HIV, therefore accrue mutations faster than viruses with DNA-based genomes. Because mutation and recombination provide the raw material...
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Components of Language01:24

Components of Language

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Language, whether spoken, signed, or written, consists of specific components: lexicon and grammar. The lexicon is the vocabulary of a language, comprising its words. Grammar is the set of rules used to convey meaning through the lexicon. For example, English grammar adds “-ed” to most verbs to indicate past tense. Words are formed by combining phonemes, which are the basic sound units of a language. Different languages have different sets of phonemes (e.g., “ah” vs.
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Language Development01:22

Language Development

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Children master language quickly and with relative ease, supported by both biological predisposition and reinforcement. B. F. Skinner (1957) proposed that language is learned through reinforcement, while Noam Chomsky (1965) argued that language acquisition mechanisms are biologically determined.
The critical period for language acquisition suggests that the ability to acquire language is at its peak early in life. As people age, this proficiency decreases. Language development begins very...
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在生物物理动力学上训练的蛋白质语言模型告知突变效应.

Chao Hou1, Haiqing Zhao2,3, Yufeng Shen1,4,5

  • 1Department of Systems Biology, Columbia University Irving Medical Center, New York, NY 10032.

Proceedings of the National Academy of Sciences of the United States of America
|January 23, 2026
PubMed
概括

SeqDance和ESMDance是新的蛋白质语言模型,使用生物物理数据捕获蛋白质动态. 这些模型改善了蛋白质行为和突变效应的预测,优于现有的方法.

关键词:
分子动力学分子动力学突变的影响 突变效应正常模式分析正常模式分析蛋白质语言模型

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科学领域:

  • 计算生物学 计算生物学
  • 结构生物学 结构生物学
  • 蛋白质动力学 蛋白质动力学

背景情况:

  • 蛋白质结构动态对于功能和突变影响至关重要.
  • 现有的深度学习模型经常忽视蛋白质动态,使用静态结构或序列.
  • 捕获蛋白质动态对于准确的功能和突变效应预测至关重要.

研究的目的:

  • 介绍SeqDance和ESMDance,这些新型的蛋白质语言模型包含了蛋白质动态.
  • 能够预测有序和无序蛋白质的动态特性.
  • 通过整合动态信息,提高突变效应的预测准确度.

主要方法:

  • 训练有素的SeqDance和ESMDance对来自分子动力学和正常模式分析超过64,000种蛋白质的动态生物物理特性进行了训练.
  • SeqDance利用注意力机制来模拟残留物移动,并编码动态表示.
  • ESMDance建立在ESM2架构之上,利用其输出进行增强的预测.

主要成果:

  • SeqDance嵌入式捕捉了丰富的蛋白质动态,使得对形状性质的转移学习成为可能.
  • SeqDance预测准确地反映了突变对蛋白质折叠稳定性的影响.
  • 对于缺乏进化数据的蛋白质,ESMDance在零射击突变效应预测方面明显优于ESM2.

结论:

  • SeqDance和ESMDance提供了一个强大的框架,用于将蛋白质动态整合到语言模型中.
  • 这些模型提供了对蛋白质行为和突变效应的更可概括的预测.
  • 开发的模型通过结合关键的动态信息,推进了蛋白质深度学习领域.