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Protein structure prediction based on Hydrophobic-Polar energy model essentially becomes searching for a conformation having a compact hydrophobic core at the center. The hydrophobic core minimizes the interaction energy between the amino…

Computational Engineering, Finance, and Science · Computer Science 2013-11-01 Swakkhar Shatabda , M. A. Hakim Newton , Duc Nghia Pham , Abdul Sattar

Predicting the three-dimensional (3D) structure of a protein from its primary sequence of amino acids is known as the protein folding (PF) problem. Due to the central role of proteins' 3D structures in chemistry, biology and medicine…

Quantum Physics · Physics 2021-03-18 Anton Robert , Panagiotis Kl. Barkoutsos , Stefan Woerner , Ivano Tavernelli

Predicting the structure of multi-protein complexes is a grand challenge in biochemistry, with major implications for basic science and drug discovery. Computational structure prediction methods generally leverage pre-defined structural…

Biomolecules · Quantitative Biology 2021-01-26 Stephan Eismann , Raphael J. L. Townshend , Nathaniel Thomas , Milind Jagota , Bowen Jing , Ron O. Dror

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

Background: In the Nearest-Neighbor Thermodynamic Model, a standard approach for RNA secondary structure prediction, the energy of the multiloops is modeled using a linear entropic penalty governed by three branching parameters. Although…

Biomolecules · Quantitative Biology 2025-10-15 Svetlana Poznanović , Owen Cardwell , Christine Heitsch

The biological functions of proteins often depend on dynamic structural ensembles. In this work, we develop a flow-based generative modeling approach for learning and sampling the conformational landscapes of proteins. We repurpose highly…

Biomolecules · Quantitative Biology 2024-09-04 Bowen Jing , Bonnie Berger , Tommi Jaakkola

Searching through chemical space is an exceptionally challenging problem because the number of possible molecules grows combinatorially with the number of atoms. Large, autoregressive models trained on databases of chemical compounds have…

Machine Learning · Computer Science 2025-10-24 Shriram Chennakesavalu , Frank Hu , Sebastian Ibarraran , Grant M. Rotskoff

Protein structure-based property prediction has emerged as a promising approach for various biological tasks, such as protein function prediction and sub-cellular location estimation. The existing methods highly rely on experimental protein…

Machine Learning · Computer Science 2023-10-20 Yufei Huang , Siyuan Li , Jin Su , Lirong Wu , Odin Zhang , Haitao Lin , Jingqi Qi , Zihan Liu , Zhangyang Gao , Yuyang Liu , Jiangbin Zheng , Stan. ZQ. Li

Atomic-accuracy structure prediction of macromolecules is a long-sought goal of computational biophysics. Accurate modeling should be achievable by optimizing a physically realistic energy function but is presently precluded by incomplete…

Biomolecules · Quantitative Biology 2011-04-29 Parin Sripakdeevong , Wipapat Kladwang , Rhiju Das

We propose and discuss a novel strategy for protein design. The method is based on recent theoretical advancements which showed the importance to treat carefully the conformational free energy of designed sequences. In this work we show how…

Statistical Mechanics · Physics 2009-10-31 A. Rossi , A. Maritan , C. Micheletti

Two proteins, one belonging to the mainly alpha class and the other belonging to the alpha/beta class, are selected to test a kinetic mechanism for protein folding. Targeted molecular dynamics is applied to generate folding pathways for…

Biological Physics · Physics 2011-01-04 Leonor Cruzeiro

The choice of structural resolution is a fundamental aspect of protein modelling, determining the balance between descriptive power and interpretability. Although atomistic simulations provide maximal detail, much of this information is…

Biomolecules · Quantitative Biology 2025-10-23 Margherita Mele , Raffaele Fiorentini , Thomas Tarenzi , Giovanni Mattiotti , Raffaello Potestio

Proteins are the basic building blocks of life. They usually perform functions by folding to a particular structure. Understanding the folding process could help the researchers to understand the functions of proteins and could also help to…

Computational Engineering, Finance, and Science · Computer Science 2015-10-21 Jianzhu Ma

Proteins are complex molecules responsible for different functions in nature. Enhancing the functionality of proteins and cellular fitness can significantly impact various industries. However, protein optimization using computational…

Machine Learning · Computer Science 2024-05-30 Minji Lee , Luiz Felipe Vecchietti , Hyunkyu Jung , Hyun Joo Ro , Meeyoung Cha , Ho Min Kim

Deep neural networks such as AlphaFold and RoseTTAFold predict remarkably accurate structures of proteins compared to other algorithmic approaches. It is known that biologically small perturbations in the protein sequence do not lead to…

Biomolecules · Quantitative Biology 2021-09-21 Sumit Kumar Jha , Arvind Ramanathan , Rickard Ewetz , Alvaro Velasquez , Susmit Jha

Modelling and predicting protein configurations is crucial for advancing drug discovery, enabling the design of treatments for life-threatening diseases. A critical aspect of this challenge is rotamer optimisation - the determination of…

Quantum Physics · Physics 2025-07-28 Anastasia Agathangelou , Dilhan Manawadu , Ivano Tavernelli

We describe a dynamic programming algorithm for predicting optimal RNA secondary structure, including pseudoknots. The algorithm has a worst case complexity of ${\cal O}(N^6)$ in time and ${\cal O}(N^4)$ in storage. The description of the…

Biological Physics · Physics 2009-09-25 Elena Rivas , Sean R. Eddy

We propose an algorithmic strategy for improving the efficiency of Monte Carlo searches for the low-energy states of proteins. Our strategy is motivated by a model of how proteins alter their shapes. In our model when proteins fold under…

Soft Condensed Matter · Physics 2009-11-07 Michael Cahill , Sean Cahill , Kevin Cahill

This paper presents a two-phase protein folding optimization on a three-dimensional AB off-lattice model. The first phase is responsible for forming conformations with a good hydrophobic core or a set of compact hydrophobic amino acid…

Neural and Evolutionary Computing · Computer Science 2020-06-30 Borko Bošković , Janez Brest

Learning meaningful protein representation is important for a variety of biological downstream tasks such as structure-based drug design. Having witnessed the success of protein sequence pretraining, pretraining for structural data which is…

Machine Learning · Computer Science 2023-02-23 Yufei Huang , Lirong Wu , Haitao Lin , Jiangbin Zheng , Ge Wang , Stan Z. Li