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Inferring the structural properties of a protein from its amino acid sequence is a challenging yet important problem in biology. Structures are not known for the vast majority of protein sequences, but structure is critical for…

Machine Learning · Computer Science 2019-10-17 Tristan Bepler , Bonnie Berger

Currently, many studies view DNA sequences as a special type of language and utilize Transformers to model them. These studies use fixed-length k-mer segmentation and BPE subword tokenization but lack a systematic evaluation to determine…

Computation and Language · Computer Science 2025-07-22 Chenlei Gong , Yuanhe Tian , Lei Mao , Yan Song

Protein representation learning methods have shown great potential to yield useful representation for many downstream tasks, especially on protein classification. Moreover, a few recent studies have shown great promise in addressing…

Machine Learning · Computer Science 2023-04-11 Can Chen , Jingbo Zhou , Fan Wang , Xue Liu , Dejing Dou

Structure-based drug design (SBDD) leverages the three-dimensional geometry of proteins to identify potential drug candidates. Traditional approaches, rooted in physicochemical modeling and domain expertise, are often resource-intensive.…

Quantitative Methods · Quantitative Biology 2024-11-19 Zaixi Zhang , Jiaxian Yan , Yining Huang , Qi Liu , Enhong Chen , Mengdi Wang , Marinka Zitnik

Coarse-graining (CG) accelerates molecular simulations of protein dynamics by simulating sets of atoms as singular beads. Backmapping is the opposite operation of bringing lost atomistic details back from the CG representation. While…

Machine Learning · Computer Science 2023-03-06 Soojung Yang , Rafael Gómez-Bombarelli

The native state structures of globular proteins are stable and well-packed indicating that self-interactions are favored over protein-solvent interactions under folding conditions. We use this as a guiding principle to derive the geometry…

Biomolecules · Quantitative Biology 2021-07-14 Tatjana Škrbić , Amos Maritan , Achille Giacometti , George D. Rose , Jayanth R. Banavar

Protein structures represent the key to deciphering biological functions. The more detailed form of similarity among these proteins is sometimes overlooked by the conventional structural comparison methods. In contrast, further advanced…

Machine Learning · Computer Science 2026-01-21 Poorya Khajouie , Titli Sarkar , Krishna Rauniyar , Li Chen , Wu Xu , Vijay Raghavan

Protein surface fingerprint encodes chemical and geometric features that govern protein-protein interactions and can be used to predict changes in binding affinity between two protein complexes. Current state-of-the-art models for…

Biomolecules · Quantitative Biology 2025-08-05 Sharmi Banerjee , Mostafa Karimi , Melih Yilmaz , Tommi Jaakkola , Bella Dubrov , Shang Shang , Ron Benson

Tokenization is widely used in large language models because it significantly improves performance. However, tokenization imposes several disadvantages, such as performance biases, increased adversarial vulnerability, decreased…

Computation and Language · Computer Science 2024-10-08 Kevin Slagle

Protein structure reconstruction from Nuclear Magnetic Resonance (NMR) experiments largely relies on computational algorithms. Recently, some effective low-rank matrix completion (MC) methods, such as ASD and ScaledASD, have been…

Biological Physics · Physics 2018-09-24 Z. Li , S. Li , X. Wei , X. Peng , Q. Zhao

We present a novel dual-head deep learning architecture for protein-protein interaction modeling that enables simultaneous prediction of binding affinity ($\Delta G$) and mutation-induced affinity changes ($\Delta\Delta G$) using only…

Quantitative Methods · Quantitative Biology 2025-09-30 Supantha Dey , Ratul Chowdhury

We present a geometry-aware method for heterogeneous single-particle cryogenic electron microscopy (cryo-EM) reconstruction that predicts atomic backbone conformations. To incorporate protein-structure priors, we represent the backbone as a…

Computer Vision and Pattern Recognition · Computer Science 2026-03-09 Jonathan Krook , Axel Janson , Joakim Andén , Melanie Weber , Ozan Öktem

Protein motifs are conserved fragments occurred frequently in protein sequences. They have significant functions, such as active site of an enzyme. Search and clustering protein sequence motifs are computational intensive. Most existing…

Genomics · Quantitative Biology 2017-01-03 Haifeng Chen , Ting Chen

The Gene or DNA sequence in every cell does not control genetic properties on its own; Rather, this is done through translation of DNA into protein and subsequent formation of a certain 3D structure. The biological function of a protein is…

Computational Engineering, Finance, and Science · Computer Science 2019-05-30 Leila Khalatbari , Mohammad Reza Kangavari , Saeid Hosseini , Hongzhi Yin , Ngai-Man Cheung

Recent advances in generative modeling show that pretrained representations can improve generation as conditioning features or alignment targets. Motivated by this, we study protein representations for predicting structures beyond…

Biomolecules · Quantitative Biology 2026-05-27 Taewon Kim , Hyosoon Jang , Hyunjin Seo , Seonghwan Seo , Hyeongwoo Kim , Wonho Zhung , Mingyeong Shin , Wooyoun Kim , Sungsoo Ahn

The potential of deep learning has been recognized in the protein structure prediction community for some time, and became indisputable after CASP13. In CASP14, deep learning has boosted the field to unanticipated levels reaching…

Biomolecules · Quantitative Biology 2021-09-14 Elodie Laine , Stephan Eismann , Arne Elofsson , Sergei Grudinin

Understanding protein sequences is vital and urgent for biology, healthcare, and medicine. Labeling approaches are expensive yet time-consuming, while the amount of unlabeled data is increasing quite faster than that of the labeled data due…

Computation and Language · Computer Science 2021-11-01 Liang He , Shizhuo Zhang , Lijun Wu , Huanhuan Xia , Fusong Ju , He Zhang , Siyuan Liu , Yingce Xia , Jianwei Zhu , Pan Deng , Bin Shao , Tao Qin , Tie-Yan Liu

Accurately predicting protein structures from amino acid sequences remains a fundamental challenge in computational biology, with profound implications for understanding biological functions and enabling structure-based drug discovery.…

Generative models have recently advanced $\textit{de novo}$ protein design by learning the statistical regularities of natural structures. However, current approaches face three key limitations: (1) Existing methods cannot jointly learn…

Machine Learning · Computer Science 2026-03-09 Zhanghan Ni , Yanjing Li , Zeju Qiu , Bernhard Schölkopf , Hongyu Guo , Weiyang Liu , Shengchao Liu

Simulating large proteins using traditional molecular dynamics (MD) is computationally demanding. To address this challenge, we propose a novel tree-structured coarse-grained model that efficiently captures protein dynamics. By leveraging a…

Chemical Physics · Physics 2024-12-11 Jinzhen Zhu