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AlphaFold can be used for both single-chain and multi-chain protein structure prediction, while the latter becomes extremely challenging as the number of chains increases. In this work, by taking each chain as a node and assembly actions as…

Computational Engineering, Finance, and Science · Computer Science 2024-05-08 Ziqi Gao , Tao Feng , Jiaxuan You , Chenyi Zi , Yan Zhou , Chen Zhang , Jia Li

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

Simple hidden Markov models are proposed for predicting secondary structure of a protein from its amino acid sequence. Since the length of protein conformation segments varies in a narrow range, we ignore the duration effect of length…

Biological Physics · Physics 2007-05-23 Wei-Mou Zheng

As high-throughput biological sequencing becomes faster and cheaper, the need to extract useful information from sequencing becomes ever more paramount, often limited by low-throughput experimental characterizations. For proteins, accurate…

Quantitative Methods · Quantitative Biology 2017-01-31 Xueliang Liu

Protein folding neural networks (PFNNs) such as AlphaFold predict remarkably accurate structures of proteins compared to other approaches. However, the robustness of such networks has heretofore not been explored. This is particularly…

Machine Learning · Computer Science 2023-01-13 Ismail Alkhouri , Sumit Jha , Andre Beckus , George Atia , Alvaro Velasquez , Rickard Ewetz , Arvind Ramanathan , Susmit Jha

High-throughput computational materials design promises to greatly accelerate the process of discovering new materials and compounds, and of optimizing their properties. The large databases of structures and properties that result from…

Chemical Physics · Physics 2016-11-22 Sandip De , Felix Musil , Teresa Ingram , Carsten Baldauf , Michele Ceriotti

Designing novel protein sequences for a desired 3D topological fold is a fundamental yet non-trivial task in protein engineering. Challenges exist due to the complex sequence--fold relationship, as well as the difficulties to capture the…

Machine Learning · Computer Science 2021-06-25 Yue Cao , Payel Das , Vijil Chenthamarakshan , Pin-Yu Chen , Igor Melnyk , Yang Shen

This paper demonstrates that language models are strong structure-based protein designers. We present LM-Design, a generic approach to reprogramming sequence-based protein language models (pLMs), that have learned massive sequential…

Machine Learning · Computer Science 2023-02-10 Zaixiang Zheng , Yifan Deng , Dongyu Xue , Yi Zhou , Fei YE , Quanquan Gu

Deep neural networks, particularly Transformers, have been widely adopted for predicting the functional properties of proteins. In this work, we focus on exploring whether Protein Transformers can capture biological intelligence among…

Machine Learning · Computer Science 2025-06-10 Fudong Lin , Wanrou Du , Jinchan Liu , Tarikul Milon , Shelby Meche , Wu Xu , Xiaoqi Qin , Xu Yuan

Protein structure prediction often hinges on multiple sequence alignments (MSAs), which underperform on low-homology and orphan proteins. We introduce PLAME, a lightweight MSA design framework that leverages evolutionary embeddings from…

Machine Learning · Computer Science 2025-09-29 Hanqun Cao , Xinyi Zhou , Zijun Gao , Chenyu Wang , Xin Gao , Zhi Zhang , Cesar de la Fuente-Nunez , Chunbin Gu , Ge Liu , Pheng-Ann Heng

Protein folding is the intricate process by which a linear sequence of amino acids self-assembles into a unique three-dimensional structure. Protein folding kinetics is the study of pathways and time-dependent mechanisms a protein undergoes…

Machine Learning · Computer Science 2023-09-19 Vijay Arvind. R , Haribharathi Sivakumar , Brindha. R

Protein structure prediction is one of the most important problems in computational biology. The most successful computational approach, also called template-based modeling, identifies templates with solved crystal structures for the query…

Biomolecules · Quantitative Biology 2013-06-20 Jian Peng

Structure determination is essential to a mechanistic understanding of diseases and the development of novel therapeutics. Machine-learning-based structure prediction methods have made significant advancements by computationally predicting…

Protein-ligand binding is the process by which a small molecule (drug or inhibitor) attaches to a target protein. Binding affinity, which characterizes the strength of biomolecular interactions, is essential for tackling diverse challenges…

Determining the structure of a protein has been a decades-long open question. A protein's three-dimensional structure often poses nontrivial computation costs, when classical simulation algorithms are utilized. Advances in the transformer…

Machine Learning · Computer Science 2023-10-09 Chen Dun , Qiutai Pan , Shikai Jin , Ria Stevens , Mitchell D. Miller , George N. Phillips, , Anastasios Kyrillidis

In cancer therapeutics, protein-metal binding mechanisms critically govern the pharmacokinetics and targeting efficacy of drugs, thereby fundamentally shaping the rational design of anticancer metallodrugs. While conventional laboratory…

Proteins, by virtue of their central role in most biological processes, represent one of the key subjects of the study of molecular evolution. Inherent to the indispensability of proteins for living cells is the fact that a given protein…

Biomolecules · Quantitative Biology 2007-05-23 Eric J. Deeds , Eugene I. Shakhnovich

Deep learning has been widely used for protein engineering. However, it is limited by the lack of sufficient experimental data to train an accurate model for predicting the functional fitness of high-order mutants. Here, we develop SESNet,…

Quantitative Methods · Quantitative Biology 2023-04-10 Mingchen Li , Liqi Kang , Yi Xiong , Yu Guang Wang , Guisheng Fan , Pan Tan , Liang Hong

Proteins are macromolecules responsible for essential functions in almost all living organisms. Designing reasonable proteins with desired functions is crucial. A protein's sequence and structure are strongly correlated and they together…

Machine Learning · Computer Science 2024-01-10 Zhenqiao Song , Yunlong Zhao , Wenxian Shi , Yang Yang , Lei Li

Advances in deep learning have opened an era of abundant and accurate predicted protein structures; however, similar progress in protein ensembles has remained elusive. This review highlights several recent research directions towards…

Biomolecules · Quantitative Biology 2025-09-23 Bowen Jing , Bonnie Berger , Tommi Jaakkola
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