水木未来·视界iss.9丨聆听真理:蛋白质折叠的"声化"研究

伊利诺伊大学香槟分校(UIUC)的一个研究小组正在利用声音来描述生物化学过程,以帮助科学家们更好地理解这些过程是如何发生的。
A team of researchers at the University of Illinois Urbana-Champaign is using sonification – the use of sound to convey information – to depict biochemical processes and better understand how they happen.
音乐教授&作曲家Stephen Andrew Taylor;美国科学院院士,化学教授&生物物理学家Martin Gruebele;以及UIUC校友、作曲家和软件设计师Carla Scaletti在UIUC组成了一个研究小组。自新冠大流行以来,他们每周都会在Zoom上开会。该小组正尝试将蛋白质音乐化,以研究蛋白质折叠的物理机制,而这项工作最近有了回报:Gruebele对蛋白质的折叠方式有了新发现。
Music professor and composer Stephen Andrew Taylor; chemistry professor and biophysicist Martin Gruebele; and Illinois music and computer science alumna, composer and software designer Carla Scaletti formed the Biophysics Sonification Group, which has been meeting weekly on Zoom since the beginning of the pandemic. The group has experimented with using sonification in Gruebele’s research into the physical mechanisms of protein folding, and its work recently allowed Gruebele to make a new discovery about the ways a protein can fold.

Taylor大部分的音乐创作都受到了科学的影响,他最近的作品融合了大量的科学数据和一些生物学过程。恰巧,Gruebele院士也是一位音乐家,他建造了自己的管风琴并将其用于自身的音乐创作。将科学事物音乐化的想法让他们产生了共鸣,并为之进行了好几年的合作。Scaletti用她名下的的公司Symbolic Sound开发了一个名为Kyma的数字音频软件和声音设计系统,该系统正被许多音乐家和研究人员使用,包括Taylor。
Taylor’s musical compositions have long been influenced by science, and recent works represent scientific data and biological processes. Gruebele also is a musician who built his own pipe organ that he plays and uses to compose music. The idea of working together on sonification struck a chord with them, and they’ve been collaborating for several years. Through her company, Symbolic Sound Corp., Scaletti develops a digital audio software and hardware sound design system called Kyma that is used by many musicians and researchers, including Taylor.

Scaletti制作了一个配音动画,用以简要说明蛋白质的折叠过程。Gruebele和Taylor用该动画来向学生介绍折叠过程中的那些关键概念,并测试该动画是否有助于学生们的理解。他们发现,将蛋白质音乐化这一举动间接加强了其结构的可视化。即使对专家们来说,音乐化也有助于提高他们对蛋白质折叠和错误折叠的理解程度。这个三人小组在《化学教育杂志》上描述了他们用音乐辅助教学的过程。DOI: 10.1021/acs.jchemed.1c00857
Scaletti created an animated visualization paired with sound that illustrated a simplified protein-folding process, and Gruebele and Taylor used it to introduce key concepts of the process to students and gauge whether it helped with their understanding. They found that sonification complemented and reinforced the visualizations and that, even for experts, it helped increase intuition for how proteins fold and misfold over time. The Biophysics Sonification Group described using sonification in teaching in the Journal of Chemical Education.
Gruebele和他的研究团队使用超级计算机对蛋白质折叠成特定结构这一复杂过程进行模拟。模拟显示了蛋白质在折叠过程中的多种途径,也显示了它们如何折叠错误或卡在错误的形状中——学界认为,这些错误与一些疾病有关,例如阿茨海默症和帕金森症。
Gruebele and his research team use supercomputers to run simulations of proteins folding into a specific structure, a process that relies on a complex pattern of many interactions. The simulation reveals the multiple pathways the proteins take as they fold, and also shows when they misfold or get stuck in the wrong shape – something thought to be related to a number of diseases such as Alzheimer’s and Parkinson’s.

(观看请配合声音)
视频一:Martin Gruebele在教学蛋白质折叠动力学的概念时
使用有声动画来描述基于简单晶格模型的状态机(state machine)
研究人员利用模拟数据来深入了解这一过程。据Gruebele说,几乎所有的数据分析都是以可视化的形式完成的,但是用计算机模拟出的大量数据可能极其难以可视化:它们包含了数十万个变量和数百万个时间戳。
The researchers use the simulation data to gain insight into the process. Nearly all data analysis is done visually, Gruebele said, but massive amounts of data generated by the computer simulations – representing hundreds of thousands of variables and millions of moments in time – can be very difficult to visualize.
Scaletti说:"在数字音频中,一切都是数据流,所以实际上,我们把数据流当作数字录音来听是很合理的。你可以听到一些看不见的东西:在数据库中的信息量如此巨大,总有一些东西是会被忽视的,但你可以用声音的形式将它们播放出来。"
“In digital audio, everything is a stream of numbers, so actually it’s quite natural to take a stream of numbers and listen to it as if it’s a digital recording,” Scaletti said. “You can hear things that you wouldn’t see if you looked at a list of numbers and you also wouldn’t see if you looked at an animation. There’s so much going on that there could be something that’s hidden, but you could bring it out with sound.”
例如,当蛋白质折叠时,它会被水分子包围,而水分子对折叠的过程至关重要。Gruebele想要知道水分子接触并将蛋白质溶解的具体时间点,但事实是,有5万个水分子在移动,其中只有一两个对溶解起到了关键的作用,以传统方法观测的话,这无异于大海捞针。然而,如果每次水分子接触到一个特定的氨基酸时,就会出现一个特殊声音的话,Gruebele就能轻易找到他想要的时间点。
For example, when the protein folds, it is surrounded by water molecules that are critical to the process. Gruebele said he wants to know when a water molecule touches and solvates a protein, but “there are 50,000 water molecules moving around, and only one or two are doing a critical thing. It’s impossible to see.” However, if a splashy sound occurred every time a water molecule touched a specific amino acid, that would be easy to hear.

(观看请配合声音)
视频二:蛋白质在进入折叠状态的过程中
会卡在局部最优解 (即局部能量最小值)
Taylor和Scaletti使用音频映射技术,将蛋白质的各个特征与声音参数联系起来,如音高、音色、响度和平移位置。例如,Taylor使用不同的音调和乐器来代表每个独特的氨基酸,以及它们的疏水性或亲水性的程度。
Taylor and Scaletti use various audio-mapping techniques to link aspects of proteins to sound parameters such as pitch, timbre, loudness and pan position. For example, Taylor’s work uses different pitches and instruments to represent each unique amino acid, as well as their hydrophobic or hydrophilic qualities.
"我试图尽可能地沿用人类对声音的本能反应,"Taylor说道,"就像贝多芬说的那样,'水流越深,音调越低'。我们认为大象会发出低沉的声音,因为它很巨大,我们也认为麻雀会发出高亢的声音,因为它很小。某些特征所对应的声音是扎根在我们的听觉认知里的。我们可以尽可能地利用这些本能认知,这有助于设计更简便的软件。
“I’ve been trying to draw on our instinctive responses to sound as much as possible,” Taylor said. “Beethoven said, ‘The deeper the stream, the deeper the tone.’ We expect an elephant to make a low sound because it’s big, and we expect a sparrow to make a high sound because it’s small. Certain kinds of mappings are built into us. As much as possible, we can take advantage of those and that helps to communicate more effectively.”
Taylor认为,音乐家高度发达的音感有助于创造“利用声音来挖掘信息”的绝佳工具:"这是利用音乐和声音来帮助我们理解世界的新方式。我想音乐家可以在这一过程中发挥重要作用。与此同时,我也在努力成为一个更好的音乐家,在以不同的方式思考声音如何以不同的方式与整个世界联系,甚至是微观世界。"
The highly developed instincts of musicians help in creating the best tool to use sound to convey information, Taylor said. “It’s a new way of showing how music and sound can help us understand the world. Musicians have an important role to play,” he said. “It’s helped me become a better musician, in thinking about sound in different ways and thinking how sound can link to the world in different ways, even the world of the very small.”
转载自: Illinois News Bureau
"Illinois musicians, chemists use sound to better understand science"
水木视界丨iss. 9

