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Generative models of macromolecules carry abundant and impactful implications for industrial and biomedical efforts in protein engineering. However, existing methods are currently limited to modeling protein structures or sequences,…

Biomolecules · Quantitative Biology 2024-01-15 Alex Morehead , Jeffrey Ruffolo , Aadyot Bhatnagar , Ali Madani

Generative models derived from large protein sequence alignments define complex fitness landscapes, but their utility for accurately modeling non-equilibrium evolutionary dynamics remains unclear. In this work, we perform a rigorous…

Populations and Evolution · Quantitative Biology 2026-02-10 Leonardo Di Bari , Thierry Mora , Andrea Pagnani , Aleksandra M. Walczak , Francesco Zamponi , Saverio Rossi

Coarse-graining (CG) enables molecular dynamics (MD) simulations of larger systems and longer timescales that are otherwise infeasible with atomistic models. Machine learning potentials (MLPs), with their capacity to capture many-body…

Chemical Physics · Physics 2025-12-01 Weilong Chen , Franz Görlich , Paul Fuchs , Julija Zavadlav

A key challenge in contrastive learning is to generate negative samples from a large sample set to contrast with positive samples, for learning better encoding of the data. These negative samples often follow a softmax distribution which…

Machine Learning · Computer Science 2024-04-17 Chung-Yiu Yau , Hoi-To Wai , Parameswaran Raman , Soumajyoti Sarkar , Mingyi Hong

We study convergence of a generative modeling method that first estimates the score function of the distribution using Denoising Auto-Encoders (DAE) or Denoising Score Matching (DSM) and then employs Langevin diffusion for sampling. We show…

Machine Learning · Statistics 2022-10-12 Adam Block , Youssef Mroueh , Alexander Rakhlin

We extend the Langevin Monte Carlo (LMC) algorithm to compactly supported measures via a projection step, akin to projected Stochastic Gradient Descent (SGD). We show that (projected) LMC allows to sample in polynomial time from a…

Probability · Mathematics 2016-08-08 Sébastien Bubeck , Ronen Eldan , Joseph Lehec

Protein sequence generation for engineering requires samples that are biophysically plausible and, when targeting a family/domain, remain recognizable members while exploring within-family diversity. Current discrete generative models…

Computational Engineering, Finance, and Science · Computer Science 2026-05-25 Langzhang Liang , Ming Yang , Yi Feng , Junfan Li , Shirui Pan , Yinghui Xu , Tianlei Ying , Yizhen Zheng , Zenglin Xu

Prompt-guided generative AI models have rapidly expanded across vision and language domains, producing realistic and diverse outputs from textual inputs. The growing variety of such models, trained with different data and architectures,…

Machine Learning · Computer Science 2026-02-09 Mehdi Lotfian , Mohammad Jalali , Farzan Farnia

We introduce Markov chain Monte Carlo (MCMC) algorithms based on numerical approximations of piecewise-deterministic Markov processes obtained with the framework of splitting schemes. We present unadjusted as well as adjusted algorithms,…

Probability · Mathematics 2025-11-04 Andrea Bertazzi , Paul Dobson , Pierre Monmarché

Domain adaptive semantic segmentation aims to generate accurate and dense predictions for an unlabeled target domain by leveraging a supervised model trained on a labeled source domain. The prevalent self-training approach involves…

Computer Vision and Pattern Recognition · Computer Science 2024-06-28 Nazanin Moradinasab , Laura S. Shankman , Rebecca A. Deaton , Gary K. Owens , Donald E. Brown

Time-resolved single-molecule biophysical experiments yield data that contain a wealth of dynamic information, in addition to the equilibrium distributions derived from histograms of the time series. In typical force spectroscopic setups…

Biomolecules · Quantitative Biology 2011-07-14 Michael Hinczewski , Yann von Hansen , Roland R. Netz

In this paper, we study the problem of sampling from a given probability density function that is known to be smooth and strongly log-concave. We analyze several methods of approximate sampling based on discretizations of the (highly…

Statistics Theory · Mathematics 2024-02-26 Arnak S. Dalalyan , Avetik G. Karagulyan

We developed a novel method based on the Fourier analysis of protein molecular surfaces to speed up the analysis of the vast structural data generated in the post-genomic era. This method computes the power spectrum of surfaces of the…

Quantitative Methods · Quantitative Biology 2015-09-18 C. Sofia Carvalho , Dimitrios Vlachakis , Georgia Tsiliki , Vasileios Megalooikonomou , Sophia Kossida

We develop a path-based approach to continuous-time random walks on networks with arbitrarily weighted edges. We describe an efficient numerical algorithm for calculating statistical properties of the stochastic path ensemble. After…

Populations and Evolution · Quantitative Biology 2014-08-19 Michael Manhart , Alexandre V. Morozov

Molecular structure generation is a fundamental problem that involves determining the 3D positions of molecules' constituents. It has crucial biological applications, such as molecular docking, protein folding, and molecular design. Recent…

Machine Learning · Computer Science 2025-08-27 Wenyin Zhou , Christopher Iliffe Sprague , Vsevolod Viliuga , Matteo Tadiello , Arne Elofsson , Hossein Azizpour

Biological machine learning is often bottlenecked by a lack of scaled data. One promising route to relieving data bottlenecks is through high throughput screens, which can experimentally test the activity of $10^6-10^{12}$ protein sequences…

Machine Learning · Statistics 2025-10-21 Eli N. Weinstein , Andrei Slabodkin , Mattia G. Gollub , Elizabeth B. Wood

In this paper we introduce a novel method of deriving a pairwise potential for protein folding. The potential is obtained by optimization procedure, which simultaneously maximizes the energy gap for {\it all} proteins in the database. To…

Condensed Matter · Physics 2007-05-23 L. A. Mirny , E. I. Shakhnovich

In this paper, we propose an efficient pseudo-marginal Markov chain Monte Carlo (MCMC) sampling approach to draw samples from posterior shape distributions for image segmentation. The computation time of the proposed approach is independent…

Computer Vision and Pattern Recognition · Computer Science 2018-09-05 Ertunc Erdil , Sinan Yildirim , Tolga Tasdizen , Mujdat Cetin

We present doubly stochastic gradient MCMC, a simple and generic method for (approximate) Bayesian inference of deep generative models (DGMs) in a collapsed continuous parameter space. At each MCMC sampling step, the algorithm randomly…

Machine Learning · Computer Science 2016-03-08 Chao Du , Jun Zhu , Bo Zhang

Inverse protein folding generates valid amino acid sequences that can fold into a desired protein structure, with recent deep-learning advances showing strong potential and competitive performance. However, challenges remain, such as…

Biomolecules · Quantitative Biology 2025-07-29 Peizhen Bai , Filip Miljković , Xianyuan Liu , Leonardo De Maria , Rebecca Croasdale-Wood , Owen Rackham , Haiping Lu