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Related papers: Evolutionary Profiles for Protein Fitness Predicti…

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Directed evolution plays an indispensable role in protein engineering that revises existing protein sequences to attain new or enhanced functions. Accurately predicting the effects of protein variants necessitates an in-depth understanding…

Quantitative Methods · Quantitative Biology 2023-06-09 Yang Tan , Bingxin Zhou , Yuanhong Jiang , Yu Guang Wang , Liang Hong

Protein Language Models (PLMs) have emerged as performant and scalable tools for predicting the functional impact and clinical significance of protein-coding variants, but they still lag experimental accuracy. Here, we present a novel…

Predicting protein stability changes induced by single-point mutations has been a persistent challenge over the years, attracting immense interest from numerous researchers. The ability to precisely predict protein thermostability is…

Biomolecules · Quantitative Biology 2023-12-08 Yijie Zhang , Zhangyang Gao , Cheng Tan , Stan Z. Li

Modern language model (LM) training has been divided into multiple stages, making it difficult for downstream developers to evaluate the impact of design choices made at each stage. We present EvoLM, a model suite that enables systematic…

Computation and Language · Computer Science 2025-11-19 Zhenting Qi , Fan Nie , Alexandre Alahi , James Zou , Himabindu Lakkaraju , Yilun Du , Eric Xing , Sham Kakade , Hanlin Zhang

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…

Machine Learning · Computer Science 2025-01-20 Yinkai Wang , Jiaxing He , Yuanqi Du , Xiaohui Chen , Jianan Canal Li , Li-Ping Liu , Xiaolin Xu , Soha Hassoun

Protein language models (pLMs), pre-trained via causal language modeling on protein sequences, have been a promising tool for protein sequence design. In real-world protein engineering, there are many cases where the amino acids in the…

Machine Learning · Computer Science 2023-03-30 Youhan Lee , Hasun Yu

Proteins, essential to biological systems, perform functions intricately linked to their three-dimensional structures. Understanding the relationship between protein structures and their amino acid sequences remains a core challenge in…

Quantitative Methods · Quantitative Biology 2024-11-04 Liang He , Peiran Jin , Yaosen Min , Shufang Xie , Lijun Wu , Tao Qin , Xiaozhuan Liang , Kaiyuan Gao , Yuliang Jiang , Tie-Yan Liu

Protein sequence design, determined by amino acid sequences, are essential to protein engineering problems in drug discovery. Prior approaches have resorted to evolutionary strategies or Monte-Carlo methods for protein design, but often…

Recent advances in Protein Language Models (PLMs) have transformed protein engineering, yet unlike their counterparts in Natural Language Processing (NLP), current PLMs exhibit a fundamental limitation: they excel in either Protein Language…

Computational Engineering, Finance, and Science · Computer Science 2025-09-16 Liuzhenghao Lv , Zongying Lin , Hao Li , Yuyang Liu , Jiaxi Cui , Calvin Yu-Chian Chen , Li Yuan , Yonghong Tian

Deep learning has transformed protein design, enabling accurate structure prediction, sequence optimization, and de novo protein generation. Advances in single-chain protein structure prediction via AlphaFold2, RoseTTAFold, ESMFold, and…

Machine Learning · Computer Science 2025-02-27 Gregory W. Kyro , Tianyin Qiu , Victor S. Batista

The structure and function of a protein are determined by its amino acid sequence. While random mutations change a protein's sequence, evolutionary forces shape its structural fold and biological activity. Studies have shown that neutral…

Biomolecules · Quantitative Biology 2024-11-15 Pranav Kantroo , Günter P. Wagner , Benjamin B. Machta

Protein language models (pLMs) pre-trained on vast protein sequence databases excel at various downstream tasks but often lack the structural knowledge essential for some biological applications. To address this, we introduce a method to…

Recent advancements in unsupervised protein language models (ProteinLMs), like ESM-1b and ESM-2, have shown promise in different protein prediction tasks. However, these models face challenges due to their high computational demands,…

Machine Learning · Computer Science 2023-10-31 Shuang Peng , Fei Yang , Ning Sun , Sheng Chen , Yanfeng Jiang , Aimin Pan

Protein mutations can have profound effects on biological function, making accurate prediction of property changes critical for drug discovery, protein engineering, and precision medicine. Current approaches rely on fine-tuning…

Machine Learning · Computer Science 2025-10-27 Srivathsan Badrinarayanan , Yue Su , Janghoon Ock , Alan Pham , Sanya Ahuja , Amir Barati Farimani

Protein language models are trained primarily with masked language modeling (MLM), which predicts amino-acid identities at masked positions. We ask whether latent-space prediction can complement these token-level objectives under matched…

Machine Learning · Computer Science 2026-05-11 Dan Ofer , Dafna Shahaf , Michal Linial

Protein language models (pLMs) have demonstrated success at generating functional proteins across vast sequence spaces but lack the ability to design high-fitness variants on demand. Here, we iteratively guide pLMs toward user-defined…

Biomolecules · Quantitative Biology 2025-12-01 Filippo Stocco , Maria Artigues-Lleixa , Andrea Hunklinger , Talal Widatalla , Marc Guell , Noelia Ferruz

Optimization modeling via mixed-integer linear programming (MILP) is fundamental to industrial planning and scheduling, yet translating natural-language requirements into solver-executable models and maintaining them under evolving business…

Artificial Intelligence · Computer Science 2026-03-24 Yiliu He , Tianle Li , Binghao Ji , Zhiyuan Liu , Di Huang

Protein language models (pLMs) produce per-residue representations that capture evolutionary and structural information, yet their mean-pooled sequence embeddings are not explicitly trained to reflect functional, evolutionary or structural…

Machine Learning · Computer Science 2026-05-11 Dan Ofer , Oriel Perets , Michal Linial , Nadav Rappoport

While protein language models (PLMs) are one of the most promising avenues of research for future de novo protein design, the way in which they transform sequences to hidden representations, as well as the information encoded in such…

Machine Learning · Computer Science 2026-05-29 Kosio Beshkov , Anders Malthe-Sørenssen

Protein language models trained on the masked language modeling objective learn to predict the identity of hidden amino acid residues within a sequence using the remaining observable sequence as context. They do so by embedding the residues…

Biomolecules · Quantitative Biology 2024-07-11 Pranav Kantroo , Günter P. Wagner , Benjamin B. Machta