Large Language Model is Secretly a Protein Sequence Optimizer
- URL: http://arxiv.org/abs/2501.09274v2
- Date: Fri, 17 Jan 2025 15:22:00 GMT
- Title: Large Language Model is Secretly a Protein Sequence Optimizer
- Authors: Yinkai Wang, Jiaxing He, Yuanqi Du, Xiaohui Chen, Jianan Canal Li, Li-Ping Liu, Xiaolin Xu, Soha Hassoun,
- Abstract summary: We consider the protein sequence engineering problem, which aims to find protein sequences with high fitness levels, starting from a given wild-type sequence.
We demonstrate large language models (LLMs), despite being trained on massive texts, are secretly protein sequences.
- Score: 24.55348363931866
- License:
- Abstract: We consider the protein sequence engineering problem, which aims to find protein sequences with high fitness levels, starting from a given wild-type sequence. Directed evolution has been a dominating paradigm in this field which has an iterative process to generate variants and select via experimental feedback. We demonstrate large language models (LLMs), despite being trained on massive texts, are secretly protein sequence optimizers. With a directed evolutionary method, LLM can perform protein engineering through Pareto and experiment-budget constrained optimization, demonstrating success on both synthetic and experimental fitness landscapes.
Related papers
- Computational Protein Science in the Era of Large Language Models (LLMs) [54.35488233989787]
Computational protein science is dedicated to revealing knowledge and developing applications within the protein sequence-structure-function paradigm.
Recently, Language Models (pLMs) have emerged as a milestone in AI due to their unprecedented language processing & generalization capability.
arXiv Detail & Related papers (2025-01-17T16:21:18Z) - SFM-Protein: Integrative Co-evolutionary Pre-training for Advanced Protein Sequence Representation [97.99658944212675]
We introduce a novel pre-training strategy for protein foundation models.
It emphasizes the interactions among amino acid residues to enhance the extraction of both short-range and long-range co-evolutionary features.
Trained on a large-scale protein sequence dataset, our model demonstrates superior generalization ability.
arXiv Detail & Related papers (2024-10-31T15:22:03Z) - Structure Language Models for Protein Conformation Generation [66.42864253026053]
Traditional physics-based simulation methods often struggle with sampling equilibrium conformations.
Deep generative models have shown promise in generating protein conformations as a more efficient alternative.
We introduce Structure Language Modeling as a novel framework for efficient protein conformation generation.
arXiv Detail & Related papers (2024-10-24T03:38:51Z) - Reinforcement Learning for Sequence Design Leveraging Protein Language Models [14.477268882311991]
We propose to use protein language models (PLMs) as a reward function to generate new sequences.
We perform extensive experiments on various sequence lengths to benchmark RL-based approaches.
We provide comprehensive evaluations along biological plausibility and diversity of the protein.
arXiv Detail & Related papers (2024-07-03T14:31:36Z) - xTrimoPGLM: Unified 100B-Scale Pre-trained Transformer for Deciphering the Language of Protein [74.64101864289572]
We propose a unified protein language model, xTrimoPGLM, to address protein understanding and generation tasks simultaneously.
xTrimoPGLM significantly outperforms other advanced baselines in 18 protein understanding benchmarks across four categories.
It can also generate de novo protein sequences following the principles of natural ones, and can perform programmable generation after supervised fine-tuning.
arXiv Detail & Related papers (2024-01-11T15:03:17Z) - Efficiently Predicting Protein Stability Changes Upon Single-point
Mutation with Large Language Models [51.57843608615827]
The ability to precisely predict protein thermostability is pivotal for various subfields and applications in biochemistry.
We introduce an ESM-assisted efficient approach that integrates protein sequence and structural features to predict the thermostability changes in protein upon single-point mutations.
arXiv Detail & Related papers (2023-12-07T03:25:49Z) - ProtFIM: Fill-in-Middle Protein Sequence Design via Protein Language
Models [0.0]
In real-world protein engineering, there are many cases where the amino acids in the middle of a protein sequence are optimized while maintaining other residues.
Protein language models (pLMs) have been a promising tool for protein sequence design.
We show that language models trained via fill-in-middle transformation, called ProtFIM, are more appropriate for protein engineering.
arXiv Detail & Related papers (2023-03-29T04:35:50Z) - Protein Sequence Design with Batch Bayesian Optimisation [0.0]
Protein sequence design is a challenging problem in protein engineering, which aims to discover novel proteins with useful biological functions.
directed evolution is a widely-used approach for protein sequence design, which mimics the evolution cycle in a laboratory environment and conducts an iterative protocol.
We propose a new method based on Batch Bayesian Optimization (Batch BO), a well-established optimization method, for protein sequence design.
arXiv Detail & Related papers (2023-03-18T14:53:20Z) - Plug & Play Directed Evolution of Proteins with Gradient-based Discrete
MCMC [1.0499611180329804]
A long-standing goal of machine-learning-based protein engineering is to accelerate the discovery of novel mutations.
We introduce a sampling framework for evolving proteins in silico that supports mixing and matching a variety of unsupervised models.
By composing these models, we aim to improve our ability to evaluate unseen mutations and constrain search to regions of sequence space likely to contain functional proteins.
arXiv Detail & Related papers (2022-12-20T00:26:23Z) - ODBO: Bayesian Optimization with Search Space Prescreening for Directed Protein Evolution [18.726398852721204]
We propose an efficient, experimental design-oriented closed-loop optimization framework for protein directed evolution.
ODBO employs a combination of novel low-dimensional protein encoding strategy and Bayesian optimization enhanced with search space prescreening via outlier detection.
We conduct and report four protein directed evolution experiments that substantiate the capability of the proposed framework for finding variants with properties of interest.
arXiv Detail & Related papers (2022-05-19T13:21:31Z) - EBM-Fold: Fully-Differentiable Protein Folding Powered by Energy-based
Models [53.17320541056843]
We propose a fully-differentiable approach for protein structure optimization, guided by a data-driven generative network.
Our EBM-Fold approach can efficiently produce high-quality decoys, compared against traditional Rosetta-based structure optimization routines.
arXiv Detail & Related papers (2021-05-11T03:40:29Z)
This list is automatically generated from the titles and abstracts of the papers in this site.
This site does not guarantee the quality of this site (including all information) and is not responsible for any consequences.