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Proteins are the fundamental macromolecules that play diverse and crucial roles in all living matter and have tremendous implications in healthcare, manufacturing, and biotechnology. Their functions are largely determined by the sequences…

Biomolecules · Quantitative Biology 2024-09-17 Boqiao Lai

Here we present an approximate analytical theory for the relationship between a protein structure's contact matrix and the shape of its energy spectrum in amino acid sequence space. We demonstrate a dependence of the number of sequences of…

Soft Condensed Matter · Physics 2009-11-07 Jeremy L. England , Eugene I. Shakhnovich

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

The remarkable structural diversity of modern proteins reflects millions of years of evolution, during which sequence space has expanded while many structural features remain conserved. This conservation is evident not only among homologous…

Scientists use mathematical modelling to understand and predict the properties of complex physical systems. In highly parameterised models there often exist relationships between parameters over which model predictions are identical, or…

Data Analysis, Statistics and Probability · Physics 2017-03-24 Dhruva V. Raman , James Anderson , Antonis Papachristodoulou

Machine learning plays an increasingly important role in computational chemistry and materials science, complementing computationally intensive ab initio and first-principles methods. Despite their utility, machine-learning models often…

Chemical Physics · Physics 2025-05-06 Makoto Takamoto , Viktor Zaverkin , Mathias Niepert

Structure prediction has become a key task of the modern atomistic sciences, and depends on the rapid and reliable computation of the energy landscape. First principles density functional based calculations are highly reliable, faithfully…

Materials Science · Physics 2022-07-08 Chris J. Pickard

Local explainability methods -- those which seek to generate an explanation for each prediction -- are becoming increasingly prevalent due to the need for practitioners to rationalize their model outputs. However, comparing local…

Machine Learning · Computer Science 2022-01-07 Peter Xenopoulos , Gromit Chan , Harish Doraiswamy , Luis Gustavo Nonato , Brian Barr , Claudio Silva

Protein sequences serve as a natural record of the evolutionary constraints that shape their functional structures. We show that it is possible to use only sequence information to go beyond predicting native structures and global stability…

Biomolecules · Quantitative Biology 2025-07-02 Ezequiel A. Galpern , Ernesto A. Roman , Diego U. Ferreiro

Designing novel functional proteins crucially depends on accurately modeling their fitness landscape. Given the limited availability of functional annotations from wet-lab experiments, previous methods have primarily relied on…

Machine Learning · Computer Science 2024-12-03 Zuobai Zhang , Pascal Notin , Yining Huang , Aurélie Lozano , Vijil Chenthamarakshan , Debora Marks , Payel Das , Jian Tang

Conventional physics-based modeling techniques involve high effort, e.g., time and expert knowledge, while data-driven methods often lack interpretability, structure, and sometimes reliability. To mitigate this, we present a data-driven…

Dynamical Systems · Mathematics 2024-08-19 Johannes Rettberg , Jonas Kneifl , Julius Herb , Patrick Buchfink , Jörg Fehr , Bernard Haasdonk

Existing methods for differentiable structure learning in discrete data typically assume that the data are generated from specific structural equation models. However, these assumptions may not align with the true data-generating process,…

Machine Learning · Computer Science 2025-10-28 Chang Deng , Bryon Aragam

Constraining the many biological parameters that govern cortical dynamics is computationally and conceptually difficult because of the curse of dimensionality. This paper addresses these challenges by proposing (1) a novel data-informed…

Neurons and Cognition · Quantitative Biology 2021-12-30 Zhuo-Cheng Xiao , Kevin K. Lin , Lai-Sang Young

Predictive coding (PC) is a biologically inspired algorithm for training neural networks that relies only on local updates, allowing parallel learning across layers. However, practical implementations face two key limitations: error signals…

Machine Learning · Computer Science 2026-03-10 Davide Casnici , Martin Lefebvre , Justin Dauwels , Charlotte Frenkel

The simulated self-assembly of molecular building blocks into functional complexes is a key area of study in computational biology and materials science. Self-assembly simulations of proteins using physically-motivated potentials for…

Soft Condensed Matter · Physics 2025-09-03 Ivan Spirandelli , Arnur Nigmetov , Dmitriy Morozov , Myfanwy E. Evans

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

The ability to computationally generate novel yet physically foldable protein structures could lead to new biological discoveries and new treatments targeting yet incurable diseases. Despite recent advances in protein structure prediction,…

Biomolecules · Quantitative Biology 2022-11-28 Kevin E. Wu , Kevin K. Yang , Rianne van den Berg , James Y. Zou , Alex X. Lu , Ava P. Amini

How do artificial neural networks bind concepts to form complex semantic structures? Here, we propose a simple neural code, whereby the existence and the type of relations between entities are represented by the distance and the direction…

Computation and Language · Computer Science 2026-05-19 Pablo J. Diego-Simón , Pierre Orhan , Emmanuel Chemla , Yair Lakretz , Jean-Rémi King

Machine learning models of materials$^{1-5}$ accelerate discovery compared to ab initio methods: deep learning models now reproduce density functional theory (DFT)-calculated results at one hundred thousandths of the cost of DFT$^{6}$. To…

Protein-protein interactions (PPIs) are fundamental to numerous cellular processes, and their characterization is vital for understanding disease mechanisms and guiding drug discovery. While protein language models (PLMs) have demonstrated…