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The goal of Protein Structure Prediction (PSP) problem is to predict a protein's 3D structure (confirmation) from its amino acid sequence. The problem has been a 'holy grail' of science since the Noble prize-winning work of Anfinsen…

Biomolecules · Quantitative Biology 2023-01-24 Abbi Abdel-Rehim , Oghenejokpeme Orhobor , Hang Lou , Hao Ni , Ross D. King

A new method for sequence optimization in protein models is presented. The approach, which has inherited its basic philosophy from recent work by Deutsch and Kurosky [Phys. Rev. Lett. 76, 323 (1996)] by maximizing conditional probabilities…

Soft Condensed Matter · Physics 2009-10-30 Anders Irbäck , Carsten Peterson , Frank Potthast , Erik Sandelin

Biological classification with interpretability remains a challenging task. For this, we introduce a novel encoding framework, Multi-Scale Reversible Chaos Game Representation (MS-RCGR), that transforms biological sequences into…

Machine Learning · Computer Science 2026-04-21 Sarwan Ali , Taslim Murad

Web crawling, snowball sampling, and respondent-driven sampling (RDS) are three types of network sampling techniques used to contact individuals in hard-to-reach populations. This paper studies these procedures as a Markov process on the…

Statistics Theory · Mathematics 2017-06-02 Karl Rohe

Protein sequence optimization under tight oracle budgets requires methods that explore vast combinatorial spaces while making each evaluation informative. Existing reinforcement learning and off-policy generative approaches often degrade…

Machine Learning · Computer Science 2026-05-27 Ashima Khanna , Dominik Grimm

Computational protein design, i.e. inferring novel and diverse protein sequences consistent with a given structure, remains a major unsolved challenge. Recently, deep generative models that learn from sequences alone or from sequences and…

Biomolecules · Quantitative Biology 2021-11-15 Igor Melnyk , Payel Das , Vijil Chenthamarakshan , Aurelie Lozano

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

This paper proposes a synergy of amortised and particle-based methods for sampling from distributions defined by unnormalised density functions. We state a connection between sequential Monte Carlo (SMC) and neural sequential samplers…

Machine Learning · Computer Science 2025-10-14 Sanghyeok Choi , Sarthak Mittal , Víctor Elvira , Jinkyoo Park , Nikolay Malkin

We present InvMSAFold, an inverse folding method for generating protein sequences that is optimized for diversity and speed. For a given structure, InvMSAFold generates the parameters of a probability distribution over the space of…

Quantitative Methods · Quantitative Biology 2025-05-30 Luca Alessandro Silva , Barthelemy Meynard-Piganeau , Carlo Lucibello , Christoph Feinauer

In the unsupervised self-evolution of Multimodal Large Language Models, the quality of feedback signals during post-training is pivotal for stable and effective learning. However, existing self-evolution methods predominantly rely on…

Computer Vision and Pattern Recognition · Computer Science 2026-04-09 Yunyao Yu , Zhengxian Wu , Zhuohong Chen , Hangrui Xu , Zirui Liao , Xiangwen Deng , Zhifang Liu , Senyuan Shi , Haoqian Wang

Multidimensional data acquisition often requires extensive time and poses significant challenges for hardware and software regarding data storage and processing. Rather than designing a single compression matrix as in conventional…

Machine Learning · Computer Science 2025-03-05 Han Wang , Eduardo Pérez , Iris A. M. Huijben , Hans van Gorp , Ruud van Sloun , Florian Römer

Given the amino acid sequence of a protein, researchers often infer its structure and function by finding homologous, or evolutionarily-related, proteins of known structure and function. Since structure is typically more conserved than…

Computational Engineering, Finance, and Science · Computer Science 2015-03-23 Noah M. Daniels

The goal of protein design is to generate amino acid sequences that fold into functional structures with desired properties. Prior methods combining autoregressive language models with Monte Carlo Tree Search (MCTS) struggle with long-range…

Machine Learning · Computer Science 2026-02-25 Xuefeng Liu , Mingxuan Cao , Songhao Jiang , Xiao Luo , Xiaotian Duan , Mengdi Wang , Tobin R. Sosnick , Jinbo Xu , Rick Stevens

Symbolic regression aims to discover human-interpretable equations that explain observational data. However, existing approaches rely heavily on discrete structure search (e.g., genetic programming), which often leads to high computational…

Machine Learning · Computer Science 2026-03-25 Fateme Memar , Tao Zhe , Dongjie Wang

Deep learning has contributed to major advances in the prediction of protein structure from sequence, a fundamental problem in structural bioinformatics. With predictions now approaching the accuracy of crystallographic resolution in some…

Quantitative Methods · Quantitative Biology 2022-01-26 Mu Gao , Mark Coletti , Russell B. Davidson , Ryan Prout , Subil Abraham , Benjamin Hernandez , Ada Sedova

While protein language models (PLMs) are one of the most promising avenues of research for future de novo protein design, the way in which they transform sequences to hidden representations, as well as the information encoded in such…

Machine Learning · Computer Science 2026-05-29 Kosio Beshkov , Anders Malthe-Sørenssen

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

The design of multi-stable RNA molecules has important applications in biology, medicine, and biotechnology. Synthetic design approaches profit strongly from effective in-silico methods, which can tremendously impact their cost and…

Quantitative Methods · Quantitative Biology 2018-06-24 Stefan Hammer , Yann Ponty , Wei Wang , Sebastian Will

Motivation: In recent years, protein function prediction has broken through the bottleneck of sequence features, significantly improving prediction accuracy using high-precision protein structures predicted by AlphaFold2. While…

Machine Learning · Computer Science 2025-04-01 Beibei Wang , Boyue Cui , Shiqu Chen , Xuan Wang , Yadong Wang , Junyi Li

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