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Existing state-of-the-art methods that take a single RNA sequence and predict the corresponding RNA secondary-structure are thermodynamic methods. These predict the most stable RNA structure, but do not consider the process of structure…

Biomolecules · Quantitative Biology 2012-07-26 Jeff R. Proctor , Irmtraud M. Meyer

Natural protein sequences somehow encode the structural forms that these molecules adopt. Recent developments in structure-prediction are agnostic to the mechanisms by which proteins fold and represent them as static objects. However, the…

Biomolecules · Quantitative Biology 2025-05-26 Ezequiel A. Galpern , Federico Caamaño , Diego U. Ferreiro

We present GridFF, an efficient method for simulating molecules on rigid substrates, derived from techniques used in protein-ligand docking in biochemistry. By projecting molecule-substrate interactions onto precomputed spatial grids with…

Chemical Physics · Physics 2025-08-22 Indranil Mal , Milan Kočí , Paolo Nicolini , Prokop Hapala

The adoption of detailed mechanisms for chemical kinetics often poses two types of severe challenges: First, the number of degrees of freedom is large; and second, the dynamics is characterized by widely disparate time scales. As a result,…

Dynamical Systems · Mathematics 2025-10-01 Eliodoro Chiavazzo , C. William Gear , Carmeline J. Dsilva , Neta Rabin , Ioannis G. Kevrekidis

A new general algorithm for optimization of potential functions for protein folding is introduced. It is based upon gradient optimization of the thermodynamic stability of native folds of a training set of proteins with known structure. The…

Condensed Matter · Physics 2009-11-10 Ole Winther , Anders Krogh

Proteins exist as a dynamic ensemble of multiple conformations, and these motions are often crucial for their functions. However, current structure prediction methods predominantly yield a single conformation, overlooking the conformational…

Biomolecules · Quantitative Biology 2025-06-18 Advaith Maddipatla , Nadav Bojan Sellam , Meital Bojan , Sanketh Vedula , Paul Schanda , Ailie Marx , Alex M. Bronstein

Among the various features of amino acids, the hydrophobic property has most visible impact on stability of a sequence folding. This is mentioned in many protein folding related work, in this paper we more elaborately discuss the…

Computational Engineering, Finance, and Science · Computer Science 2013-12-16 Geetika Silakari Pandey , R. C. Jain

Learning effective protein representations is critical in a variety of tasks in biology such as predicting protein function or structure. Existing approaches usually pretrain protein language models on a large number of unlabeled amino acid…

Machine Learning · Computer Science 2023-01-31 Zuobai Zhang , Minghao Xu , Arian Jamasb , Vijil Chenthamarakshan , Aurelie Lozano , Payel Das , Jian Tang

We propose a new way of looking at global optimization of off-lattice protein models. We present a dual optimization concept of predicting optimal sequences as well as optimal folds. We validate the utility of the recently introduced…

Computational Physics · Physics 2012-05-22 István Kolossváry , Kevin J. Bowers

Small-molecule foundation models are typically pretrained on standalone molecular data, unlike vision and language models that often benefit from cross-modal or relational supervision. Protein-ligand co-folding provides a molecular analogue…

Biomolecules · Quantitative Biology 2026-05-25 Hyosoon Jang , Hyunjin Seo , Honghui Kim , Seonghyun Park , Taewon Kim , Yunhui Jang , Sungsoo Ahn

Electrostatic forces play many important roles in molecular biology, but are hard to model due to the complicated interactions between biomolecules and the surrounding solvent, a fluid composed of water and dissolved ions. Continuum model…

Numerical Analysis · Mathematics 2015-12-29 Jaydeep P. Bardhan , Matthew G. Knepley

Computer modeling of multicellular systems has been a valuable tool for interpreting and guiding in vitro experiments relevant to embryonic morphogenesis, tumor growth, angiogenesis and, lately, structure formation following the printing of…

Biological Physics · Physics 2015-05-28 Elijah Flenner , Lorant Janosi , Bogdan Barz , Adrian Neagu , Gabor Forgacs , Ioan Kosztin

The evolutionary trajectory of a protein through sequence space is constrained by function and three-dimensional (3D) structure. Residues in spatial proximity tend to co-evolve, yet attempts to invert the evolutionary record to identify…

Biomolecules · Quantitative Biology 2015-03-13 Debora S. Marks , Lucy J. Colwell , Robert Sheridan , Thomas A. Hopf , Andrea Pagnani , Riccardo Zecchina , Chris Sander

Proteins and other macromolecules exist not in a single state but as dynamic ensembles of interconverting conformations, which are essential for catalysis, allosteric regulation, and molecular recognition. While AI-based structure…

Biomolecules · Quantitative Biology 2025-10-22 Stephanie A. Wankowicz , Massimiliano Bonomi

A comparative classification scheme provides a good basis for several approaches to understand proteins, including prediction of relations between their structure and biological function. But it remains a challenge to combine a…

Biomolecules · Quantitative Biology 2015-05-20 Shuangwei Hu , Andrei Krokhotin , Antti J. Niemi , Xubiao Peng

For many membrane proteins the determination of their topology remains a challenge for methods like X-ray crystallography and nuclear magnetic resonance (NMR) spectroscopy. Electron paramagnetic resonance (EPR) spectroscopy has evolved as…

The computational design of novel protein structures has the potential to impact numerous scientific disciplines greatly. Toward this goal, we introduce FoldFlow, a series of novel generative models of increasing modeling power based on the…

Molecular property prediction, crucial for early drug candidate screening and optimization, has seen advancements with deep learning-based methods. While deep learning-based methods have advanced considerably, they often fall short in fully…

Biomolecules · Quantitative Biology 2024-07-01 Taojie Kuang , Yiming Ren , Zhixiang Ren

Recent works have shown the promise of learning pre-trained models for 3D molecular representation. However, existing pre-training models focus predominantly on equilibrium data and largely overlook off-equilibrium conformations. It is…

Chemical Physics · Physics 2023-08-30 Rui Feng , Qi Zhu , Huan Tran , Binghong Chen , Aubrey Toland , Rampi Ramprasad , Chao Zhang

We introduce IntFold, a controllable foundation model for general and specialized biomolecular structure prediction. Utilizing a high-performance custom attention kernel, IntFold achieves accuracy comparable to the state-of-the-art…

Biomolecules · Quantitative Biology 2025-07-08 The IntFold Team , Leon Qiao , Wayne Bai , He Yan , Gary Liu , Nova Xi , Xiang Zhang , Siqi Sun
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