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An unsolved challenge in the development of antigen specific immunotherapies is determining the optimal antigens to target. Comprehension of antigen-MHC binding is paramount towards achieving this goal. Here, we present CASTELO, a combined…

Quantitative Methods · Quantitative Biology 2020-12-09 David Bell , Giacomo Domeniconi , Chih-Chieh Yang , Ruhong Zhou , Leili Zhang , Guojing Cong

A small model polypeptide represented in atomic detail is folded using Monte Carlo dynamics. The polypeptide is designed to have a native conformation similar to the central part of the helix-turn-helix protein ROP. Starting from a…

Biological Physics · Physics 2008-02-03 D. Hoffmann , E. W. Knapp

Generating large ensembles of candidate conformations is standard for improving biomolecular structure prediction. Yet aimless sampling is inefficient and costly, producing many redundant conformations with limited diversity, so additional…

Biomolecules · Quantitative Biology 2025-10-21 Lihang Liu , Yang Liu , Xianbin Ye , Shanzhuo Zhang , Yuxin Li , Kunrui Zhu , Yang Xue , Xiaonan Zhang , Xiaomin Fang

Learning how proteins fold will hardly have any impact in the way conventional -- active site centered -- drugs are designed. On the other hand, this knowledge is proving instrumental in defining a new paradigm for the identification of…

Biomolecules · Quantitative Biology 2012-03-16 R. A. Broglia

Protein-ligand complex structures have been utilised to design benchmark machine learning methods that perform important tasks related to drug design such as receptor binding site detection, small molecule docking and binding affinity…

Biomolecules · Quantitative Biology 2021-08-26 Rishal Aggarwal , Akash Gupta , U Deva Priyakumar

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

Investigating conformational landscapes of proteins is a crucial way to understand their biological functions and properties. AlphaFlow stands out as a sequence-conditioned generative model that introduces flexibility into structure…

Machine Learning · Computer Science 2024-07-18 Shaoning Li , Mingyu Li , Yusong Wang , Xinheng He , Nanning Zheng , Jian Zhang , Pheng-Ann Heng

Aptamers are single stranded DNA, RNA or peptide sequences having the ability to bind a variety of specific targets (proteins, molecules as well as ions). Therefore, aptamer production and selection for therapeutic and diagnostic…

Biomolecules · Quantitative Biology 2018-01-04 R. Cataldo , E. Alfinito , L. Reggiani

One of the main problems of drug design is that of optimizing the drug--target interaction. In the case in which the target is a viral protein displaying a high mutation rate, a second problem arises, namely the eventual development of…

Biomolecules · Quantitative Biology 2007-05-23 R. A. Broglia , G. Tiana , L. Sutto , D. Provasi , F. Simona

There are numerous peptides discovered through past decades, which exhibit antimicrobial and anti-cancerous tendencies. Due to these reasons, peptides are supposed to be sound therapeutic candidates. Some peptides can pose low metabolic…

Machine Learning · Computer Science 2020-12-14 Ali Raza , Hafiz Saud Arshad

Protein structure prediction models such as AlphaFold3 (AF3) push the frontier of biomolecular modeling by incorporating science-informed architectural changes to the transformer architecture. However, these advances come at a steep system…

Biomolecules · Quantitative Biology 2025-06-27 Hoa La , Ahan Gupta , Alex Morehead , Jianlin Cheng , Minjia Zhang

Predicting how a drug-like molecule binds to a specific protein target is a core problem in drug discovery. An extremely fast computational binding method would enable key applications such as fast virtual screening or drug engineering.…

Biomolecules · Quantitative Biology 2022-06-07 Hannes Stärk , Octavian-Eugen Ganea , Lagnajit Pattanaik , Regina Barzilay , Tommi Jaakkola

Small molecule drug design hinges on obtaining co-crystallized ligand-protein structures. Despite AlphaFold2's strides in protein native structure prediction, its focus on apo structures overlooks ligands and associated holo structures.…

Biological Physics · Physics 2024-07-08 Xinyu Gu , Akashnathan Aranganathan , Pratyush Tiwary

We introduce a generative model for protein backbone design utilizing geometric products and higher order message passing. In particular, we propose Clifford Frame Attention (CFA), an extension of the invariant point attention (IPA)…

Machine Learning · Computer Science 2024-11-11 Simon Wagner , Leif Seute , Vsevolod Viliuga , Nicolas Wolf , Frauke Gräter , Jan Stühmer

Recent developments in specialized computer hardware have greatly accelerated atomic level Molecular Dynamics (MD) simulations. A single GPU-attached cluster is capable of producing microsecond-length trajectories in reasonable amounts of…

Quantitative Methods · Quantitative Biology 2018-06-01 Yunlong Liu , L. Mario Amzel

The evolution of drug-resistant microbial species is one of the major challenges to global health. The development of new antimicrobial treatments such as antimicrobial peptides needs to be accelerated to combat this threat. However, the…

Biomolecules · Quantitative Biology 2019-11-15 Sadaf Gull , Fayyaz Minhas

Highly accurate biomolecular structure prediction is a key component of developing biomolecular foundation models, and one of the most critical aspects of building foundation models is identifying the recipes for scaling the model. In this…

Biomolecules · Quantitative Biology 2026-01-02 Yi Zhou , Chan Lu , Yiming Ma , Wei Qu , Fei Ye , Kexin Zhang , Lan Wang , Minrui Gui , Quanquan Gu

Peptide self-assembly prediction offers a powerful bottom-up strategy for designing biocompatible, low-toxicity materials for large-scale synthesis in a broad range of biomedical and energy applications. However, screening the vast sequence…

Biomolecules · Quantitative Biology 2026-04-23 Nuno Costa , Julija Zavadlav

The asymmetric Hopfield model is used to simulate signaling dynamics in gene/transcription factor networks. The model allows for a direct mapping of a gene expression pattern into attractor states. We analyze different control strategies…

Molecular Networks · Quantitative Biology 2014-10-09 Anthony Szedlak , Giovanni Paternostro , Carlo Piermarocchi

We study the relation between $\alpha$-helix formation and folding for a simple artificial peptide, Ala$_{10}$-Gly$_5$-Ala$_{10}$. Our data rely on multicanonical Monte Carlo simulations where the interactions among all atoms are taken into…

Statistical Mechanics · Physics 2009-11-07 Nelson A. Alves , Ulrich H. E. Hansmann