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Markov state models (MSMs) are valuable for studying dynamics of protein conformational changes via statistical analysis of molecular dynamics (MD) simulations. In MSMs, the complex configuration space is coarse-grained into conformational…

Biological Physics · Physics 2024-06-11 Dedi Wang , Yunrui Qiu , Eric Beyerle , Xuhui Huang , Pratyush Tiwary

Representation learning and \emph{de novo} generation of proteins are pivotal computational biology tasks. Whilst natural language processing (NLP) techniques have proven highly effective for protein sequence modelling, structure modelling…

Quantitative Methods · Quantitative Biology 2025-01-08 Benoit Gaujac , Jérémie Donà , Liviu Copoiu , Timothy Atkinson , Thomas Pierrot , Thomas D. Barrett

Designing DNA and protein sequences with improved function has the potential to greatly accelerate synthetic biology. Machine learning models that accurately predict biological fitness from sequence are becoming a powerful tool for…

Machine Learning · Computer Science 2022-03-17 Johannes Linder , Georg Seelig

We resolve difficulties in training and sampling from a discrete generative model by learning a smoothed energy function, sampling from the smoothed data manifold with Langevin Markov chain Monte Carlo (MCMC), and projecting back to the…

Cis-regulatory modules (CRMs) composed of multiple transcription factor binding sites (TFBSs) control gene expression in eukaryotic genomes. Comparative genomic studies have shown that these regulatory elements are more conserved across…

Applications · Statistics 2007-09-14 Qing Zhou , Wing Hung Wong

This dissertation explores how deep generative models can advance the analysis of challenging biological problems by integrating domain knowledge with deep learning. It focuses on two areas: DNA reaction kinetics and cryogenic electron…

Machine Learning · Computer Science 2026-05-07 Chenwei Zhang

In this study, we propose a Kernel-PCA model designed to capture structure-function relationships in a protein. This model also enables ranking of reaction coordinates according to their impact on protein properties. By leveraging machine…

Computation and Language · Computer Science 2025-03-26 Parisa Mollaei , Amir Barati Farimani

Enzyme engineering enables the modification of wild-type proteins to meet industrial and research demands by enhancing catalytic activity, stability, binding affinities, and other properties. The emergence of deep learning methods for…

Computation and Language · Computer Science 2024-10-29 Yang Tan , Ruilin Wang , Banghao Wu , Liang Hong , Bingxin Zhou

Macroscopic dynamical descriptions of complex physical systems are crucial for understanding and controlling material behavior. With the growing availability of data and compute, machine learning has become a promising alternative to…

Computational Physics · Physics 2026-03-24 Mengyi Chen , Pengru Huang , Kostya S. Novoselov , Qianxiao Li

In this paper, we propose a probabilistic physics-guided framework, termed Physics-guided Deep Markov Model (PgDMM). The framework targets the inference of the characteristics and latent structure of nonlinear dynamical systems from…

Machine Learning · Computer Science 2022-05-26 Wei Liu , Zhilu Lai , Kiran Bacsa , Eleni Chatzi

Despite recent advances in protein-ligand structure prediction, deep learning methods remain limited in their ability to accurately predict binding affinities, particularly for novel protein targets dissimilar from the training set. In…

Quantitative Methods · Quantitative Biology 2025-12-04 Michael Brocidiacono , James Wellnitz , Konstantin I. Popov , Alexander Tropsha

Protein folding is the intricate process by which a linear sequence of amino acids self-assembles into a unique three-dimensional structure. Protein folding kinetics is the study of pathways and time-dependent mechanisms a protein undergoes…

Machine Learning · Computer Science 2023-09-19 Vijay Arvind. R , Haribharathi Sivakumar , Brindha. R

Molecular dynamics (MD) has become a powerful tool for studying biophysical systems, due to increasing computational power and availability of software. Although MD has made many contributions to better understanding these complex…

Computational Physics · Physics 2019-09-27 Yihang Wang , Joao Marcelo Lamim Ribeiro , Pratyush Tiwary

A Restricted Boltzmann Machine (RBM) is an unsupervised machine-learning bipartite graphical model that jointly learns a probability distribution over data and extracts their relevant statistical features. As such, RBM were recently…

Machine Learning · Computer Science 2019-02-19 Jérôme Tubiana , Simona Cocco , Rémi Monasson

The detection of change-points in heterogeneous sequences is a statistical challenge with many applications in fields such as finance, signal analysis and biology. A wide variety of literature exists for finding an ideal set of…

Applications · Statistics 2012-12-11 The Minh Luong , Vittorio Perduca , Gregory Nuel

Protein engineering is experiencing a paradigmatic shift through the integration of geometric deep learning into computational design workflows. While traditional strategies, such as rational design and directed evolution, have enabled…

Predicting protein stability changes induced by single-point mutations has been a persistent challenge over the years, attracting immense interest from numerous researchers. The ability to precisely predict protein thermostability is…

Biomolecules · Quantitative Biology 2023-12-08 Yijie Zhang , Zhangyang Gao , Cheng Tan , Stan Z. Li

Disordered proteins play essential roles in myriad cellular processes, yet their structural characterization remains a major challenge due to their dynamic and heterogeneous nature. We here present a community-driven initiative to address…

We propose a Bayesian hidden Markov model for analyzing time series and sequential data where a special structure of the transition probability matrix is embedded to model explicit-duration semi-Markovian dynamics. Our formulation allows…

Methodology · Statistics 2022-05-23 Beniamino Hadj-Amar , Jack Jewson , Mark Fiecas

Living systems rely on coordinated molecular interactions, especially those related to gene expression and protein activity. The Unfolded Protein Response is a crucial mechanism in eukaryotic cells, activated when unfolded proteins exceed a…

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