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High-quality training datasets are crucial for the development of effective protein design models, but existing synthetic datasets often include unfavorable sequence-structure pairs, impairing generative model performance. We leverage…

Protein design has become a critical method in advancing significant potential for various applications such as drug development and enzyme engineering. However, protein design methods utilizing large language models with solely pretraining…

Artificial Intelligence · Computer Science 2024-12-06 Xiao-Yu Guo , Yi-Fan Li , Yuan Liu , Xiaoyong Pan , Hong-Bin Shen

We consider molecule generation in 3D space using language models (LMs), which requires discrete tokenization of 3D molecular geometries. Although tokenization of molecular graphs exists, that for 3D geometries is largely unexplored. Here,…

Artificial Intelligence · Computer Science 2024-08-20 Xiner Li , Limei Wang , Youzhi Luo , Carl Edwards , Shurui Gui , Yuchao Lin , Heng Ji , Shuiwang Ji

Proteins are responsible for the most diverse set of functions in biology. The ability to extract information from protein sequences and to predict the effects of mutations is extremely valuable in many domains of biology and medicine.…

Quantitative Methods · Quantitative Biology 2018-01-04 Sam Sinai , Eric Kelsic , George M. Church , Martin A. Nowak

Protein structure prediction is a challenging and unsolved problem in computer science. Proteins are the sequence of amino acids connected together by single peptide bond. The combinations of the twenty primary amino acids are the…

Computational Engineering, Finance, and Science · Computer Science 2015-10-12 Mahmood A. Rashid , Firas Khatib , Abdul Sattar

Accurately modeling and designing protein complex structures is a central problem in computational structural biology, with broad implications for understanding cellular function and developing therapeutics. This thesis investigates two…

Machine Learning · Computer Science 2026-05-13 Ziwei Xie

The prediction of protein structures from sequences is an important task for function prediction, drug design, and related biological processes understanding. Recent advances have proved the power of language models (LMs) in processing the…

Quantitative Methods · Quantitative Biology 2022-12-01 Bozhen Hu , Jun Xia , Jiangbin Zheng , Cheng Tan , Yufei Huang , Yongjie Xu , Stan Z. Li

Recent computational advances in the accurate prediction of protein three-dimensional (3D) structures from amino acid sequences now present a unique opportunity to decipher the interrelationships between proteins. This task entails--but is…

Biomolecules · Quantitative Biology 2020-05-19 Menuka Jaiswal , Saad Saleem , Yonghyeon Kweon , Eli J Draizen , Stella Veretnik , Cameron Mura , Philip E. Bourne

Memory retention mechanisms play a central role in determining the efficiency of computational architectures designed for processing extended sequences. Conventional methods for token management often impose fixed retention thresholds or…

Computation and Language · Computer Science 2025-03-26 Jonathan Delena , Augustin Moreau , Dominic Ravensdale , Frederick Chatterton

While conventional methods for sequential learning focus on interaction between consecutive inputs, we suggest a new method which captures composite semantic flows with variable-length dependencies. In addition, the semantic structures…

Machine Learning · Computer Science 2019-01-29 Kyoung-Woon On , Eun-Sol Kim , Yu-Jung Heo , Byoung-Tak Zhang

Determining the different conformational states of a protein and the transition paths between them is key to fully understanding the relationship between biomolecular structure and function. This can be accomplished by sampling protein…

Biological Physics · Physics 2021-03-24 Venkata K. Ramaswamy , Chris G. Willcocks , Matteo T. Degiacomi

The design of novel proteins has many applications but remains an attritional process with success in isolated cases. Meanwhile, deep learning technologies have exploded in popularity in recent years and are increasingly applicable to…

Biomolecules · Quantitative Biology 2018-11-07 Joe G Greener , Lewis Moffat , David T Jones

Standard language models employ unique, monolithic embeddings for each token, potentially limiting their ability to capture the multifaceted nature of word meanings. We investigate whether tokens can be more effectively represented through…

Computation and Language · Computer Science 2025-09-24 Kavin R , Pawan Goyal

An approach that combines Self-Organizing maps, hierarchical clustering and network components is presented, aimed at comparing protein conformational ensembles obtained from multiple Molecular Dynamic simulations. As a first result the…

Computational Engineering, Finance, and Science · Computer Science 2013-10-01 Domenico Fraccalvieri , Laura Bonati , Fabio Stella

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

Dynamic probabilistic networks are a compact representation of complex stochastic processes. In this paper we examine how to learn the structure of a DPN from data. We extend structure scoring rules for standard probabilistic networks to…

Artificial Intelligence · Computer Science 2013-02-01 Nir Friedman , Kevin Murphy , Stuart Russell

We review the recent progress in computational approaches to protein design which builds on advances in statistical-mechanical protein folding theory. In particular, we evaluate the degeneracy of the protein code (i.e. how many sequences…

Condensed Matter · Physics 2007-05-23 E. I. Shakhnovich

Achieving a comprehensive understanding of the behaviour of proteins is greatly facilitated by the knowledge of their structures, thermodynamics and dynamics. All this information can be provided in an effective manner in terms of…

Quantitative Methods · Quantitative Biology 2019-03-27 Massimiliano Bonomi , Michele Vendruscolo

Large scale initiatives such as the Human Genome Project, Structural Genomics, and individual research teams have provided large deposits of genomic and proteomic data. The transfer of data to knowledge has become one of the existing…

Databases · Computer Science 2019-11-21 Casey A Cole , Christopher Ott , Diego Valdes , Homayoun Valafar

Massive molecular simulations of drug-target proteins have been used as a tool to understand disease mechanism and develop therapeutics. This work focuses on learning a generative neural network on a structural ensemble of a drug-target…

Machine Learning · Computer Science 2022-05-24 N. Joseph Tatro , Payel Das , Pin-Yu Chen , Vijil Chenthamarakshan , Rongjie Lai