doi.bio/esm3/esm3.intro.full9

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The proteins that exist today have developed into their present forms over the course of billions of years of natural evolution, passing through a vast evolutionary sieve

This sentence means that the proteins we have today have gone through a long process of change and development over a very long time. This process is called natural evolution and it has helped to shape the proteins into their current forms. The phrase "passing through a vast evolutionary sieve" means that many different factors have influenced the development of these proteins over time, and only the ones that were best suited to their environment were able to survive and continue to evolve.

In parallel experiments conducted over geological time, nature creates random mutations and applies selection, filtering proteins by their myriad sequences, structures, and functions

This sentence is talking about how nature creates and selects proteins over a very long period of time. It does this by making random changes to the proteins and then choosing the ones that work best. The proteins are chosen based on their different shapes, structures, and functions. This process has been happening for millions of years and is still happening today.

As a result, the patterns in the proteins we observe reflect the action of the deep hidden variables of the biology that have shaped their evolution across time

This sentence is saying that the patterns we see in proteins are influenced by the underlying biological processes that have changed over time. These processes are not immediately visible, but they have an impact on the way proteins develop and evolve.

Gene sequencing surveys of Earth's natural diversity are cataloging the sequences $(1-3)$ and structures $(4,5)$ of proteins, containing billions of sequences and hundreds of millions of structures that illuminate patterns of variation across life

Gene sequencing surveys are studies that examine the genetic makeup of different organisms on Earth. These studies are creating a catalog of the sequences and structures of proteins, which are important building blocks of life. The catalog contains billions of sequences and hundreds of millions of structures, which provide valuable information about the diversity of life on our planet. By analyzing this information, scientists can identify patterns of variation across different species and gain insights into how organisms have evolved over time.

A consensus is building that underlying these sequences is a fundamental language of protein biology that can be understood using large language models (6-10)

This sentence suggests that there is a growing agreement among experts that there is a basic language of protein biology that can be understood by using large language models. The sentence is likely referring to the use of computational models to analyze and understand the sequences of amino acids that make up proteins. The idea is that by studying these sequences, researchers can gain insights into the structure and function of proteins, which are essential for many biological processes. The use of large language models is a relatively new approach to this kind of analysis, and it is seen as a promising way to uncover new insights into protein biology.

A number of language models of protein sequences have now been developed and evaluated ( $9,11-14$ )

This sentence is about a topic related to protein sequences. It says that there are now several models that have been created and tested to understand protein sequences. The numbers in parentheses refer to other studies or sources that have been used to support this claim.

It has been found that the representations that emerge within language models reflect the biological structure and function of proteins $(6,15,16)$, and are learned without any supervision on those properties, improving with scale $(5,17,18)$

This sentence means that when language models are used to study proteins, they can create representations that accurately reflect the structure and function of those proteins. This happens without any guidance or input from experts, and the accuracy of these representations improves as more data is analyzed.

In artificial intelligence, scaling laws have been found that predict the growth in capabilities with increasing scale, describing a frontier in compute, parameters and data (19-21)

In the field of artificial intelligence, researchers have discovered patterns or rules called "scaling laws" that can predict how much better AI systems will become as they get bigger and more complex. These scaling laws can help us understand how much computing power, data, and other resources we need to achieve certain levels of AI performance. By studying these scaling laws, we can better plan and design AI systems that are more efficient and effective.

We present ESM3, a frontier multimodal generative model, that reasons over the sequences, structures, and functions of proteins

ESM3 is a new type of computer program that can analyze and understand the different parts of proteins, such as their sequences, structures, and functions. It is called a "multimodal generative model" because it can work with different types of data and create new examples of proteins based on what it has learned. This program is very advanced and can help scientists better understand how proteins work in the body.

ESM3 is trained as a generative masked language model over discrete tokens for each modality

Sure, I'd be happy to help!

This sentence is describing a type of machine learning model called ESM3, which stands for "Embed, Segment, and Merge." ESM3 is a type of model that can understand and generate text, images, and other types of data.

The sentence says that ESM3 is "trained as a generative masked language model over discrete tokens for each modality." This means that the model is designed to generate new data by predicting what comes next in a sequence of words or other data points. The "masked" part means that some of the data points are hidden or "masked" during training, which helps the model learn to predict what comes next based on the context of the surrounding data.

The "discrete tokens" part means that the model works with individual data points, like words or pixels in an image, rather than continuous data like audio or video. And the "for each modality" part means that the model can work with different types of data, like text, images, and audio, all using the same underlying structure.

Overall, this sentence is describing a powerful and flexible machine learning model that can be used for a wide range of tasks, from generating text to analyzing images and more.

Structural reasoning is achieved by encoding three-dimensional atomic structure as discrete tokens rather than with the complex architecture and diffusion in three-dimensional space employed in recent predictive (22) and generative models $(14,23-25)$ of proteins

The sentence is discussing how to represent the three-dimensional structure of atoms in a way that can be easily understood by a computer program. The traditional approach has been to use complex mathematical models that simulate the movement of atoms in three-dimensional space. However, the sentence suggests that a new approach, called "structural reasoning," is more effective. This approach involves breaking down the three-dimensional structure into smaller, more manageable parts, which can be represented using simple tokens. This makes it easier for computer programs to understand and work with the structure. The sentence also mentions that this new approach has been shown to be more accurate than previous methods in predicting the structure of proteins.

All-to-all modeling of discrete tokens is scalable, and allows ESM3 to be prompted with any combination of its modalities, enabling controllable generation of new proteins that respect combinations of prompts

This sentence is discussing a computer program called ESM3, which is used to generate new proteins. The sentence is saying that ESM3 can be used to create proteins that have specific characteristics, and that it can do this by combining different types of information (called "modalities"). The sentence also says that ESM3 can be used to create proteins that have certain combinations of characteristics, and that this can be done by "prompting" the program with specific information. Finally, the sentence says that ESM3 is able to handle a large amount of information ("scalable"), and that it can be used to create proteins that have any combination of characteristics that the user wants.

ESM3 at its largest scale was trained with $1

This sentence is about a machine learning model called ESM3, which was trained using a large amount of data. The "$1" at the end of the sentence is likely a typo or a mistake, as it doesn't seem to have any meaning in this context.###

07 \times 10^{24}$ FLOPs on 2

This sentence is discussing the amount of computing power used to perform a task. FLOPs stands for "floating-point operations per second" and is a measure of how many calculations a computer can perform in one second. The number 07 \times 10^{24} means 7 followed by 24 zeros, which is a very large number. So, the sentence is saying that a computer performed 7 x 10^24 FLOPs on 2, which means it did a lot of calculations on a specific task.###

78 billion proteins and 771 billion unique tokens, and has 98 billion parameters

This sentence is describing the size and complexity of a machine learning model. The model has 78 billion proteins and 771 billion unique tokens, which are the building blocks of the model. It also has 98 billion parameters, which are the adjustable values that the model uses to make predictions or decisions. This is a very large and complex model, which means it can handle a lot of data and make very accurate predictions.

Scaling ESM3 to this 98 billion parameter size results in improvements in the representation of sequence, structure, and function, as well as on generative evaluations

This sentence is discussing the benefits of increasing the size of a model called ESM3 to 98 billion parameters. The increase in size leads to improvements in the model's ability to represent sequences, structures, and functions, as well as its performance on generative evaluations. In simpler terms, the larger model is better at understanding and generating complex data.

We find that ESM3 is highly responsive to prompts, and finds creative solutions to complex combinations of prompts, including solutions for which we can find no matching structure in nature

The sentence means that ESM3 is a system that can quickly and effectively respond to different types of prompts or instructions. It is also able to come up with unique and innovative solutions to complex problems, even if those solutions have not been seen before in nature.

We find that models at all scales can be aligned to better follow prompts

This sentence means that the models at different levels can be adjusted to better match the instructions given. It is a technical statement that suggests that the models can be improved to better fit the requirements of the task at hand.

Larger models are far more responsive to alignment, and

show greater capability to solve the hardest prompts after alignment

This sentence is saying that when larger models are aligned properly, they are better able to handle difficult tasks. Alignment refers to the process of making sure that the model is properly set up and configured to perform the task at hand. When larger models are aligned correctly, they are more responsive and capable of solving difficult problems. This is because larger models have more processing power and can handle more complex tasks.

We report the generation of a new green fluorescent protein (GFP) with ESM3

This sentence is about the creation of a new type of green fluorescent protein (GFP) that has been given the name ESM3. GFP is a protein that is commonly used in scientific research to help visualize cells and other biological structures. The new ESM3 GFP is a variation of the original GFP that has been modified to have different properties, such as a different color or brightness. The sentence is likely part of a scientific paper or report that is discussing the development and testing of this new protein.

User:

Fluorescent proteins are responsible for the glowing colors of jellyfish and corals (26) and are important tools in modern biotechnology (27)

Fluorescent proteins are special types of proteins that can emit light, which is why they are responsible for the bright and glowing colors seen in jellyfish and corals. These proteins are also very useful in modern biotechnology, which is the field of science that uses living organisms or their parts to create useful products or technologies. In biotechnology, fluorescent proteins are used as markers or tags to help scientists track and study other proteins or cells.

They share an elegant structure: an eleven stranded beta barrel with a helix that threads its center, which scaffolds the formation of a light-emitting chromophore out of the protein's own atoms

This sentence is describing the structure of a protein. It has a specific shape called an "eleven stranded beta barrel" and a helix that runs through the center of it. This structure helps to create a special part of the protein called a "chromophore" which can emit light. The chromophore is made up of atoms that are part of the protein itself.

This mechanism is unique in nature-no other protein spontaneously forms a fluorescent chromophore out of its own structure-suggesting that producing fluorescence is hard even for nature

This sentence is saying that there is a special process in nature where a protein can create its own fluorescent substance without any help from other things. This is very rare and unusual because it's the only protein that can do this on its own. This means that making something glow in the dark is difficult, even for nature.

Our new protein, which we have named esmGFP, has $36 \%$ sequence identity to Aequorea victoria GFP, and $58 \%$ sequence identity to the most similar known fluorescent protein

We have discovered a new protein that we named esmGFP. It is similar to another protein called Aequorea victoria GFP, but only by 36%. However, it is more similar to another known fluorescent protein, with a similarity of 58%.

Despite GFP's intense focus as a target for protein engineering over several decades, as far as we are aware, proteins this distant have only been found through the discovery of new GFPs in nature

This sentence is saying that even though scientists have been studying a protein called GFP (green fluorescent protein) for a long time and trying to change it in different ways, they have only found proteins that are very different from GFP by discovering new types of GFP in nature.

Similar amounts of diversification among natural GFPs have occurred over predictable timescales

This sentence is saying that the amount of variety or differences among natural GFPs (green fluorescent proteins) has happened in a way that can be expected or predicted over a certain period of time.

Understood in these terms, the generation of a new fluorescent protein at this distance from existing proteins appears to be equivalent to simulating over 500 million years of evolution

This sentence means that creating a new fluorescent protein that is different from existing proteins is similar to the process of evolution that would take a very long time, around 500 million years, to occur naturally.

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