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Deep learning has transformed protein design, enabling accurate structure prediction, sequence optimization, and de novo protein generation. Advances in single-chain protein structure prediction via AlphaFold2, RoseTTAFold, ESMFold, and…

Machine Learning · Computer Science 2025-02-27 Gregory W. Kyro , Tianyin Qiu , Victor S. Batista

This work explores an extension of machine learning-optimized piecewise polynomial approximation by incorporating energy optimization as an additional objective. Traditional closed-form solutions enable continuity and approximation targets…

Machine Learning · Computer Science 2025-08-08 Hannes Waclawek , Stefan Huber

The search for binary sequences with low peak sidelobe level value represents a formidable computational problem. To locate better sequences for this problem, we designed a stochastic algorithm that uses two fitness functions. In these…

Artificial Intelligence · Computer Science 2024-06-12 Borko Bošković , Janez Brest

A Monte Carlo method for dynamics simulation of all-atom protein models is introduced, to reach long times not accessible to conventional molecular dynamics. The considered degrees of freedom are the dihedrals at C$_\alpha$-atoms. Two Monte…

chem-ph · Physics 2009-10-28 Daniel Hoffmann , Ernst-Walter Knapp

In spite of decades of research, much remains to be discovered about folding: the detailed structure of the initial (unfolded) state, vestigial folding instructions remaining only in the unfolded state, the interaction of the molecule with…

Biological Physics · Physics 2018-11-26 Walter A. Simmons

Lattice protein folding models are a cornerstone of computational biophysics. Although these models are a coarse grained representation, they provide useful insight into the energy landscape of natural proteins. Finding low-energy…

The recent breakthrough of AlphaFold3 in modeling complex biomolecular interactions, including those between proteins and ligands, nucleotides, or metal ions, creates new opportunities for protein design. In so-called inverse protein…

Biomolecules · Quantitative Biology 2025-07-22 Kai Yi , Kiarash Jamali , Sjors H. W. Scheres

Protein folding is a problem of large interest since it concerns the mechanism by which the genetic information is translated into proteins with well defined three-dimensional (3D) structures and functions. Recently theoretical models have…

Biomolecules · Quantitative Biology 2007-05-23 Emidio Capriotti , Rita Casadio

Protein folding and design are major biophysical problems, the solution of which would lead to important applications especially in medicine. Here a novel protein model capable of simultaneously provide quantitative protein design and…

Biological Physics · Physics 2015-06-22 Ivan Coluzza

An effective potential function is critical for protein structure prediction and folding simulation. Simplified protein models such as those requiring only $C_\alpha$ or backbone atoms are attractive because they enable efficient search of…

Biomolecules · Quantitative Biology 2007-05-23 Jinfeng Zhang , Rong Chen , Jie Liang

We significantly improve known time bounds for solving the minimum cut problem on undirected graphs. We use a ``semi-duality'' between minimum cuts and maximum spanning tree packings combined with our previously developed random sampling…

Data Structures and Algorithms · Computer Science 2007-05-23 David R. Karger

We propose a model that explains the hierarchical organization of proteins in fold families. The model, which is based on the evolutionary selection of proteins by their native state stability, reproduces patterns of amino acids conserved…

Statistical Mechanics · Physics 2007-05-23 Nikolay V. Dokholyan , Eugene I. Shakhnovich

Long chains of the HP lattice protein model are studied by the Multi-Self-Overlap Ensemble(MSOE) Monte Carlo method, which was developed recently by the authors. MSOE successfully finds the lowest energy states reported before for sequences…

Soft Condensed Matter · Physics 2009-10-31 George Chikenji , Macoto Kikuchi , Yukito Iba

The computation of the global minimum energy conformation (GMEC) is an important and challenging topic in structure-based computational protein design. In this paper, we propose a new protein design algorithm based on the AND/OR…

Artificial Intelligence · Computer Science 2015-01-16 Yichao Zhou , Yuexin Wu , Jianyang Zeng

Computational protein design has a wide variety of applications. Despite its remarkable success, designing a protein for a given structure and function is still a challenging task. On the other hand, the number of solved protein structures…

Quantitative Methods · Quantitative Biology 2018-04-26 Jingxue Wang , Huali Cao , John Z. H. Zhang , Yifei Qi

Fragment-based assembly has been widely used in Ab initio protein folding simulation which can effectively reduce the conformational space and thus accelerate sampling. The efficiency of fragment-based movement as well as the quality of…

Quantitative Methods · Quantitative Biology 2019-06-14 Tong Wang , Haipeng Gong , Eugene I. Shakhnovich

Protein structure prediction often hinges on multiple sequence alignments (MSAs), which underperform on low-homology and orphan proteins. We introduce PLAME, a lightweight MSA design framework that leverages evolutionary embeddings from…

Machine Learning · Computer Science 2025-09-29 Hanqun Cao , Xinyi Zhou , Zijun Gao , Chenyu Wang , Xin Gao , Zhi Zhang , Cesar de la Fuente-Nunez , Chunbin Gu , Ge Liu , Pheng-Ann Heng

Designing novel protein sequences for a desired 3D topological fold is a fundamental yet non-trivial task in protein engineering. Challenges exist due to the complex sequence--fold relationship, as well as the difficulties to capture the…

Machine Learning · Computer Science 2021-06-25 Yue Cao , Payel Das , Vijil Chenthamarakshan , Pin-Yu Chen , Igor Melnyk , Yang Shen

Designing protein sequences with desired biological function is crucial in biology and chemistry. Recent machine learning methods use a surrogate sequence-function model to replace the expensive wet-lab validation. How can we efficiently…

Biomolecules · Quantitative Biology 2024-12-04 Zhenqiao Song , Lei Li

For the vast majority of naturally occurring, small, single domain proteins folding is often described as a two-state process that lacks detectable intermediates. This observation has often been rationalized on the basis of a nucleation…

Biomolecules · Quantitative Biology 2007-07-09 R. D. M. Travasso , P. F. N. Faisca , M. M. Telo da Gama
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