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Three-dimensional molecular generators based on diffusion models can now reach near-crystallographic accuracy, yet they remain fragmented across tasks. SMILES-only inputs, two-stage pretrain-finetune pipelines, and one-task-one-model…

Biomolecules · Quantitative Biology 2025-07-11 Dong Xu , Zhangfan Yang , Sisi Yuan , Jenna Xinyi Yao , Jiangqiang Li , Junkai Ji

Simulating large-scale protein dynamics using traditional all-atom molecular dynamics (MD) remains computationally prohibitive. We present a unified, universal framework for coarse-grained molecular dynamics (CG-MD) that achieves…

Atomic Physics · Physics 2026-04-16 Jinzhen Zhu

Computational protein design (CPD) refers to the use of computational methods to design proteins. Traditional methods relying on energy functions and heuristic algorithms for sequence design are inefficient and do not meet the demands of…

Machine Learning · Computer Science 2024-10-30 Xiaoqi Ling , Cheng Cai , Demin Kong , Zhisheng Wei , Jing Wu , Lei Wang , Zhaohong Deng

Deep learning in \emph{de novo} protein design has achieved atomic-level fidelity. However, existing models remain largely non-deliberative: they directly synthesize molecular geometries without explicitly reasoning about which residues or…

We present a detailed study of the performance and reliability of design procedures based on energy minimization. The analysis is carried out for model proteins where exact results can be obtained through exhaustive enumeration. The…

Statistical Mechanics · Physics 2007-05-23 Cristian Micheletti , Amos Maritan

Protein design is a fundamental challenge in biotechnology, aiming to design novel sequences with specific functions within the vast space of possible proteins. Recent advances in deep generative models have enabled function-based protein…

Machine Learning · Computer Science 2025-10-15 Nuowei Liu , Jiahao Kuang , Yanting Liu , Tao Ji , Changzhi Sun , Man Lan , Yuanbin Wu

Designing novel proteins with desired functions is crucial in biology and chemistry. However, most existing work focus on protein sequence design, leaving protein sequence and structure co-design underexplored. In this paper, we propose…

Machine Learning · Computer Science 2023-10-05 Zhenqiao Song , Yunlong Zhao , Yufei Song , Wenxian Shi , Yang Yang , Lei Li

Proteins are essential macromolecules defined by their amino acid sequences, which determine their three-dimensional structures and, consequently, their functions in all living organisms. Therefore, generative protein modeling necessitates…

Machine Learning · Computer Science 2024-10-18 Xinyou Wang , Zaixiang Zheng , Fei Ye , Dongyu Xue , Shujian Huang , Quanquan Gu

Computational protein design (CPD) offers transformative potential for bioengineering, but current deep CPD models, focused on universal domains, struggle with function-specific designs. This work introduces a novel CPD paradigm tailored…

Quantitative Methods · Quantitative Biology 2024-11-28 Jiangbin Zheng , Ge Wang , Han Zhang , Stan Z. Li

While DeepMind has tentatively solved protein folding, its inverse problem -- protein design which predicts protein sequences from their 3D structures -- still faces significant challenges. Particularly, the lack of large-scale standardized…

Quantitative Methods · Quantitative Biology 2022-02-15 Zhangyang Gao , Cheng Tan , Stan Z. Li

The present paper is devoted to foundations of p-adic modelling in genomics. Considering nucleotides, codons, DNA and RNA sequences, amino acids, and proteins as information systems, we have formulated the corresponding p-adic formalisms…

Other Quantitative Biology · Quantitative Biology 2010-12-01 Branko Dragovich , Alexandra Dragovich

In recent years, there has been a surge in the development of 3D structure-based pre-trained protein models, representing a significant advancement over pre-trained protein language models in various downstream tasks. However, most existing…

Machine Learning · Computer Science 2024-06-04 Jiale Zhao , Wanru Zhuang , Jia Song , Yaqi Li , Shuqi Lu

Reliable evaluation of protein structure predictions remains challenging, as metrics like pLDDT capture energetic stability but often miss subtle errors such as atomic clashes or conformational traps reflecting topological frustration…

We introduce a protein language model for determining the complete sequence of a peptide based on measurement of a limited set of amino acids. To date, protein sequencing relies on mass spectrometry, with some novel edman degregation based…

In this paper it is shown that within a Combined Genetic Code Table, realized through a combination of Watson-Crick Table and Codon Path Cube it exists, without an exception, a strict distinction between two classes of enzymes…

Genomics · Quantitative Biology 2007-05-23 Miloje M. Rakocevic

Protein design has the potential to revolutionize biotechnology and medicine. While most efforts have focused on proteins with well-defined structures, increased recognition of the functional significance of intrinsically disordered…

Biomolecules · Quantitative Biology 2025-09-17 Giulio Tesei , Francesco Pesce , Kresten Lindorff-Larsen

Antibody design remains a critical challenge in therapeutic and diagnostic development, particularly for complex antigens with diverse binding interfaces. Current computational methods face two main limitations: (1) capturing geometric…

Machine Learning · Computer Science 2025-06-27 Jiameng Chen , Xiantao Cai , Jia Wu , Wenbin Hu

Recent studies have shown competitive performance in protein design that aims to find the amino acid sequence folding into the desired structure. However, most of them disregard the importance of predictive confidence, fail to cover the…

Biomolecules · Quantitative Biology 2023-05-31 Zhangyang Gao , Cheng Tan , Stan Z. Li

Innovations like protein diffusion have enabled significant progress in de novo protein design, which is a vital topic in life science. These methods typically depend on protein structure encoders to model residue backbone frames, where…

Computational Engineering, Finance, and Science · Computer Science 2023-10-19 Weian Mao , Muzhi Zhu , Zheng Sun , Shuaike Shen , Lin Yuanbo Wu , Hao Chen , Chunhua Shen

In recent years, deep learning techniques have made significant strides in molecular generation for specific targets, driving advancements in drug discovery. However, existing molecular generation methods present significant limitations:…

Machine Learning · Computer Science 2025-03-12 Taojie Kuang , Qianli Ma , Athanasios V. Vasilakos , Yu Wang , Qiang , Cheng , Zhixiang Ren