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Many biologically important ligands of proteins are large, flexible, and often charged molecules that bind to extended regions on the protein surface. It is infeasible or expensive to locate such ligands on proteins with standard methods…

A single gene can encode for different protein versions through a process called alternative splicing. Since proteins play major roles in cellular functions, aberrant splicing profiles can result in a variety of diseases, including cancers.…

Genomics · Quantitative Biology 2021-03-09 Alvin Chan , Anna Korsakova , Yew-Soon Ong , Fernaldo Richtia Winnerdy , Kah Wai Lim , Anh Tuan Phan

Diffusion generative models have emerged as a powerful framework for addressing problems in structural biology and structure-based drug design. These models operate directly on 3D molecular structures. Due to the unfavorable scaling of…

Biomolecules · Quantitative Biology 2024-05-10 Ian Dunn , David Ryan Koes

Energy landscape theory describes how a full-length protein can attain its native fold after sampling only a tiny fraction of all possible structures. Although protein folding is now understood to be concomitant with synthesis on the…

Biomolecules · Quantitative Biology 2013-10-17 David S. Tourigny

Discrete diffusion or flow models could enable faster and more controllable sequence generation than autoregressive models. We show that na\"ive linear flow matching on the simplex is insufficient toward this goal since it suffers from…

Biomolecules · Quantitative Biology 2024-06-03 Hannes Stark , Bowen Jing , Chenyu Wang , Gabriele Corso , Bonnie Berger , Regina Barzilay , Tommi Jaakkola

Recent advancements in the ability to construct three-dimensional (3D) tissues and organoids from stem cells and biomaterials have not only opened abundant new research avenues in disease modeling and regenerative medicine but also have…

Tissues and Organs · Quantitative Biology 2017-07-27 Richard J. McMurtrey

Allosteric interactions in DNA are crucial for various biological processes. These interactions are quantified by measuring the change in free energy as a function of the distance between the binding sites for two ligands. Here we show that…

Biological Physics · Physics 2018-05-15 Jaspreet Singh , Prashant K. Purohit

We present an investigation into diffusion models for molecular generation, with the aim of better understanding how their predictions compare to the results of physics-based calculations. The investigation into these models is driven by…

We employ simulations of model proteins to study folding on rugged energy landscapes. We construct ``first-passage'' networks as the system transitions from unfolded to native states. The nodes and bonds in these networks correspond to…

Soft Condensed Matter · Physics 2015-05-13 Gregg Lois , J. Blawzdziewicz , Corey S. O'Hern

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

The ability to significantly enhance energy transfer processes at the nanoscale requires the simultaneous optimization of molecular-scale orientation and macroscopic photonic enhancement between multiple quantum emitters. However, achieving…

The two strands of a DNA molecule with a repetitive sequence can pair into many different basepairing patterns. For perfectly periodic sequences, early bulk experiments of Poerschke indicate the existence of a sliding process, permitting…

Biomolecules · Quantitative Biology 2007-05-23 Richard A. Neher , Ulrich Gerland

We report a study of DNA (150 bp fragments) conformations in very low added salt $<0.05$mM, across wide DNA concentration range $0.0015\leq c \leq 8$~mM (bp). We found an intermediate DNA conformation in the region $0.05 < c < 1$~mM, by…

Integrative biomolecular modeling of RNA relies on structural refined collections and accurate experimental data that reflect binding and folding behavior. However, the prediction of such collections remains challenging due to the rugged…

Transcription is the first step of gene expression, in which a particular segment of DNA is copied to RNA by the enzyme RNA polymerase (RNAP). Despite many details of the complex interactions between DNA and RNA synthesis disclosed…

Biological Physics · Physics 2020-02-17 Xining Xu , Yunxin Zhang

The speed of site-specific binding of transcription factor (TFs) proteins with genomic DNA seems to be strongly retarded by the randomly occurring sequence traps. Traps are those DNA sequences sharing significant similarity with the…

Subcellular Processes · Quantitative Biology 2016-07-22 G. Niranjani , R. Murugan

Proper folding of deeply knotted proteins has a very low success rate even in structure-based models which favor formation of the native contacts but have no topological bias. By employing a structure-based model, we demonstrate that…

Biological Physics · Physics 2015-09-04 Mateusz Chwastyk , Marek Cieplak

In this work, we show that by varying the experimental conditions, the driving amplitude, a dynamic force microscope allows DNA properties to be selectively imaged. The substrate on which the DNA is fixed is a silica surface grafted with…

Biological Physics · Physics 2016-08-16 Laurent Nony , Rodolphe Boisgard , Jean-Pierre Aimé

The diffusion of particles in complex media has gained significant interest due to its dual relevance: probing the viscoelastic properties of materials via microrheology and assessing the extent of particle displacement over time. In this…

Soft Condensed Matter · Physics 2025-06-24 Fabian A. Garcia Daza , Alvaro Rodriguez-Rivas , Fernando Govantes , Alejandro Cuetos

Transcription factors are proteins that regulate the expression of genes by binding to specific genomic regions known as Transcription Factor Binding Sites (TFBSs), typically located in the promoter regions of those genes. Accurate…

Machine Learning · Computer Science 2025-02-04 Nimisha Ghosh , Pratik Dutta , Daniele Santoni