【全浸导读】Proteinotopia蛋白折叠众生

全浸阅读=Total Immerse Dynamic eReading=TIDE

Biological origami: Proteinotopia

Remarkable progress has been made in understanding the folding of proteins. It will help open up almost limitless vistas

▷origami-the Japanese art of folding paper into attractive shapes

▷proteinotopia=protein+otopia(alltopia错位)

▷limitless vistas

vista-a beautiful view

蛋白折叠出众生？

P1

WHEN ST JOHN THE EVANGELIST wrote of the Word becoming Flesh, he was drawing on ideas of reason and order derived from classical Greek philosophy. But he was also providing a succinct description of the most basic truth in molecular biology. In a wonderful and ancient mechanism called the ribosome, words—in the form of messages stored in DNA—are translated into flesh, in the form of proteins.

▷The evangelist-a person who tries to persuade people to become Christians, especially by travelling around the country holding religious meetings or speaking on radio or television

▷wrote of the Word becoming Flesh

"In the beginning was the Word and the Word was with God, and the Word was God."The Word was God and the Word became flesh. If the Word was God and the Word became flesh, then God became flesh. God became human.”

这是教义，无资格解释，下附简短注释，大家可自行了解

What Does John Mean by the 'Word Became Flesh’?John, the son of Zebedee wrote the gospel according to John. He was one of the original twelve disciples, and his audience originally consisted of both Jews and Gentiles in and around Ephesus. In John's Gospel, he describes who Jesus is and what He has done.“And the Word became flesh and dwelt among us, and we have seen his glory, glory as of the only Son from the Father, full of grace and truth.”When John says the “Word became flesh,” he is referring to God taking on humanity through Jesus. This means that Jesus is eternally one with God (John 1:1-2) and reveals the Father to us as the only begotten Son (John 3:16). The event John is describing in John 1:14 is the most spectacular event in history. God—being completely just, holy, sovereign, infinite, loving, and omnipresent—clothed Himself in humanity and lived among us in Jesus, as one who is both God and man (John 1:18). The “Word became flesh” not only means that Jesus is fully God and fully man but implies that Jesus has fulfilled all Old Testament prophecies.

▷drawing an ideas of reason and order derived from classical Greek philosophy 这一句写文章特别是论文时引用别人作品的时候可以借用

*derive from-come from, get from

▷provide a succint description of the most basic truth

*succint-marked by compact precise expression without wasted words

▷ribosome 核糖

▷molecular biology 分子生物

▷words—in the form of messages stored in DNA—are translated into flesh, in the form of proteins

开篇借用一个宗教典故，word类比DNA， flesh类比protein的关系

这一句教义描述的是人类历史发展的大奇迹，用以类比这个remarkable progress， which might be promising in open up almost limitless vistas

对这个进展的期望与定位是相当的高。

P2

Proteins are flesh both literally, in that they give meat the texture and bloodiness that carnivores savour, and figuratively, in that their actions lie behind all the strengths and frailties of body and mind. Both their manipulation and their mass production are fundamental to modern pharmacology. The huge market for statins rests on the way they interact with the workings of a protein called HMG-CoAreductase; Keytruda, the world’s biggest-selling cancer drug, is a protein itself, a subtly tweaked antibody which turns off a mechanism that lets cancers evade the immune system. Understanding the form and function of proteins is crucial to medicine, to agriculture and to replacing the petrochemicals currently produced from oil. And that understanding is fast deepening.

▷literally字面的...figuratively比喻的

▷carnivores savour

carnivore-any animal that eats meat

savour-enjoy the full taste or flavour of something, especially by eating or drinking it slowly这一句同时也是人造肉的精髓

▷strengths and frailties of body and mind

strength vs frailties(weakness)

▷manipulation

-behaviour that controls or influences somebody/something, often in a dishonest way so that they do not realize it

▷pharmacology-the scientific study of drugs and their use in medicine

▷statins

-alsoknownasHMGCoAreductaseinhibitors,areaclassoflipid-loweringmedications.Statinshavebeenfoundtoreducecardiovasculardisease(CVD)andmortalityinthosewhoareathighriskofcardiovasculardisease.

他汀类药物，即3-羟基-3甲基戊二酰辅酶A（HMG-CoA）还原酶抑制药，不仅能强效地降低总胆固醇（TC）和低密度脂蛋白（LDL），而且能一定程度上降低三酰甘油(TG)，还能升高高密度脂蛋白(HDL)，所以他汀类药物也可以称为较全面的调脂药,现已成为冠心病预防和治疗的最有效药物。近年来，研究发现他汀类药物具有多方面非降脂作用，其中包括抑制动脉粥样硬化与血栓形成，还具有缓解器官移植后的排异反应、治疗骨质疏松症、抗肿瘤、抗老年痴呆等多种作用

▷rest on-to depend or rely on somebody/something

▷reductase-还原酶

▷turns off a mechanism that lets cancers evade the immune system

科学文章中常有此类结构，有点类似否定之否定，

关掉那个能让癌细胞从免疫系统逃逸的机制=让癌细胞无处可逃

这种用法不是为了强调，而是科学研究发现就是如此，阅读时需要小心

✍Both their(protein) manipulation and their mass production are fundamental to modern pharmacology.

p3

Proteins are created as chains of smaller molecules called amino acids. The ribosome can fill each link in the chain with one of 20 different varieties of them. The words stored in DNA set out which of those 20 types of amino acid goes where. The process is explained in this week’s “Biology brief”, the first of six.

P4

In order to take on the shape required of it, a protein must fold itself up into a specific form, a process which produces all manner of kinks, twists, swirls, sheets and cavities. The shape depends on the amino-acid sequence, but the interactions between the hundreds of amino acids are just too complex for the sequence alone to reveal much. To understand the structure of a protein in detail, scientists have had to make comparatively large amounts of it, coax those molecules into forming a crystal (or, more recently, flash-freeze them) and bombard the sample with X-rays (or, if it is a frozen one, electrons). These procedures take time, money and effort. Only a tiny fraction of the proteins whose sequences are known have been studied this way.

▷kinks, twists,swirls, sheets, and cavities, 回应文章开头的proteinotopia，

以及origami, 蛋白质像一个体操运动员一样柔软多变，做出各种动作满足DNA中的携带的"word"发出的指令， kinks-bend，twist，swirls-move around, sheets-expand into sheets， cavities-make holes

是不是像艺术体操proteinotopia或者日本折纸origami？

▷flash freeze-freeze very quickly

▷bombard-fire large guns or drop bomb

✍TheStudy of the struture take time, money and effort

P5

Now things look likely to get considerably easier. AlphaFold, a very elegant piece of software developed by DeepMind, a British AIcompany, has learned from the detailed study of sequence and structure to make predictions of protein shapes using just the amino-acid sequences of their very bendy backbones. On July 22nd DeepMind, which, like Google, is owned by Alphabet, made 350,000 of its predictions freely available to all, having released the code the week before. Millions more such predictions are expected soon.

▷very bendy backbone-折叠的蛋白质骨架链

✍Alphafold makes the study easier.

P6

As those suspicious of hype rightly point out, not all of these will be equally good and better prediction does not do away with the need for other ways of exploring protein structure. AlphaFold will not be the last word in the application of AI to the problem. All that said, the software looks likely to be massively useful, helping researchers spot possibilities and dead ends more quickly and letting them take on projects they would otherwise have steered clear of. If AlphaFold is not soon providing useful pharmacological results, as well as lots of basic biology, it will not be for want of application.

▷suspicious of hype

hype-advertisements and discussion on television, radio, etc. telling the public about a product and about how good or important it is

▷do away with-to kill/get rid of

▷spot possiblities and deadends

▷steer clear of-avoid

✍Alphafold is not the only solution but likely to be massively helpful

P7

AlphaFold will also help usher in an era of altogether stranger things. Proteins are typically made from 20 different amino acids, each of which can, in principle, sit at any point in the chain. With 20 choices as to what should follow the first amino acid, you have 20x20=400 possible amino-acid doublets, 20x20x20=8,000 triplets and so on. By the time you get to an eight-amino-acid chain, there are more possibilities than there are people on Earth. Human proteins are typically 400 amino acids long; many have lengths in the thousands. There is no type of physical thing in the observable universe remotely as numerous as the possibilities inherent in a 400-amino-acid protein.

▷help usher in

usher-a person who shows people where to sit in a church, public hall, etc.

✍Alphafold help usher in an era of altogether strange things

P8

The “potential protein space” such calculations reveal is thus a cosmos unto itself, ordered yet near infinite. The bit that evolution has explored so far—which contains wonders as diverse as proteins that flex like springs, spin like wheels, extend like pistons and crank like ratchets, that turn sunlight into chemical energy, that build, demolish and recycle all the components of life and do more besides—is but the tiniest corner of it. Already some scientists are working on “de novo” proteins well outside nature’s comfort zone as ways of making tiny mechanisms and machines. As tools like AlphaFold increase the ease of molecular design, they will be joined by many more.

▷a cosmos unto itself-unto=to

▷flex like springs, spin like wheels, extend like pistons and crank like ratchets(棘轮) 回应前文的In order to take on the shape required of it, a protein must fold itself up into a specific form, a process which produces all manner of kinks, twists, swirls, sheets and cavities.

▷do more besides-do more than above mentioned

▷de novo-De novo:拉丁文,从头开始的意思,de nove测序则是指在不需要任何参考序列的情况下对某一物种进行基因组测序,然后将测得的序列进行拼接、组装,从而绘制该物种的全基因组序列图谱。

✍What Alfafold help done is just but the tiniest corner of the protein "cosmo"

P9

Compared with the designs evolution has honed over billions of years such things as this will be the crudest of toys, at least to begin with. But who can say what new flesh the designers’ words will eventually bring into being? ■

▷the crudest of toys

crude-simply made, not showing much skill or attention to detail

✍But who can say what new flesh the designers' words will eventually bring into being? 回应开头的宗教类比，designer是双关的，being也是相关的，人类越接近真相， 科学与宗教的边界就越模糊