J. N. Onuchic

Regulation of chromatin transcription dynamics by DNA supercoiling

This paper models chromatin torsion and RNAP translocation to show how DNA supercoiling and nucleosome dynamics regulate transcription velocity and gene expression.

RACER-m Leverages Structural Features for Sparse T Cell Specificity Prediction

RACER-m predicts T cell specificity using structural features, requiring fewer training examples than sequence-based methods.

Temporally correlated active forces drive segregation and enhanced dynamics in chromosome polymers

The paper models chromosome polymers with active forces, showing activity drives segregation and dynamic compaction, and alters compartmental organization.

An Associative Memory Hamiltonian Model for DNA and Nucleosomes

This paper introduces a computational model called WEChroM to simulate DNA and nucleosome mechanics, showing it can reproduce DNA structure, supercoiling behavior, and nucleosome unwrapping.

Structural Reorganization and Relaxation Dynamics of Axially Stressed Chromosomes

This study uses a coarse-grained polymer model to simulate mitotic chromosome mechanics, finding they are ten times stiffer than interphase chromosomes and exhibit viscoelastic behavior.

Shaping the Genome via Lengthwise Compaction, Phase Separation, and Lamina Adhesion

The paper develops a polymer model of the genome to explore how physical interactions shape genome architecture across species.

Examining the Ensembles of Amyloid-β Monomer Variants and their Propensities to Form Fibers Using an Energy Landscape Visualization Method

This study uses ELViM to analyze Aβ40 and Aβ42 monomers and their mutations, showing how ELViM distinguishes fiber-forming from non-fiber-forming variants.

Apropos of Universal Epitope Discovery for COVID-19 Vaccines: A Framework for Targeted Phage Display-Based Delivery and Integration of New Evaluation Tools

The paper describes a framework using targeted phage display to identify conserved epitopes on the SARS-CoV-2 Spike protein for universal vaccine development.

SMOG 2 and OpenSMOG: Extending the limits of structure-based models

This paper introduces SMOG 2 and OpenSMOG, extending structure-based models to handle large biomolecular systems with enhanced customization and integration with OpenMM.

Nrf2 modulates the hybrid epithelial/mesenchymal phenotype and Notch signaling during collective cancer migration

This study shows Nrf2 stabilizes hybrid epithelial/mesenchymal cells and coordinates Notch signaling during collective cancer migration.

Evolutionary differences in the ACE2 reveals the molecular origins of COVID-19 susceptibility

The paper uses energy landscape theory to analyze ACE2 protein sequences across animals, identifying patterns that correlate with susceptibility to COVID-19.

Design and proof-of-concept for targeted phage-based COVID-19 vaccination strategies with a streamlined cold-free supply chain

This paper designs and evaluates phage-based and AAVP-based vaccination strategies for SARS-CoV-2 that induce systemic antibody responses in mice, with potential for a cold-free supply chain.

DNA supercoiling-mediated collective behavior of co-transcribing RNA polymerases

The paper presents a theoretical model showing DNA supercoiling mediates long-range cooperation between co-transcribing RNA polymerases, affecting transcription elongation rates and orientation-dependent interactions.

Exploring Energy Landscapes of Intrinsically Disordered Proteins: Insights into Functional Mechanisms

This paper introduces ELViM, a reaction coordinate-free method to analyze energy landscapes of IDPs, revealing conformational differences between phosphoforms of PAGE4.

Sterically-Confined Rearrangements of SARS-CoV-2 Spike Protein Control Cell Invasion

This study shows that glycosylation on SARS-CoV-2 Spike protein delays conformational changes, allowing fusion peptides to bind host membranes, thereby facilitating viral entry.

Rapid Assessment of T-Cell Receptor Specificity of the Immune Repertoire

This paper introduces RACER, a pairwise energy model that assesses TCR-peptide affinity using supervised machine learning, demonstrating its utility in simulating thymic selection and estimating recognition rates for tumor antigens.

Exploring Chromosomal Structural Heterogeneity AcrossMultiple Cell Lines

The paper uses simulations and machine learning to predict chromosomal structures across cell lines, showing consistency with microscopy and revealing conformational transitions and compartment rearrangements.

Enhancing Intracellular Accumulation and Target Engagement of PROTACs with Reversible Covalent Chemistry

This study discovers that reversible covalent chemistry enhances PROTAC intracellular accumulation and target engagement, leading to improved efficacy.

Modeling Mayaro and Chikungunya Control Strategies in Rio de Janeiro Outbreaks

The paper analyzes Chikungunya outbreaks in Rio de Janeiro using a compartmental model to estimate the basic reproduction number and simulate public intervention scenarios for Mayaro virus.

A biophysical model uncovers the size distribution of migrating cell clusters across cancer types

This paper develops a biophysical model to explain cancer cell migration modes, showing that partial EMT and cooperative mechanisms can generate cluster size distributions observed across cancer types.

NRF2 activates a partial Epithelial-Mesenchymal Transition and is maximally present in a hybrid Epithelial/Mesenchymal phenotype

This study shows NRF2 stabilizes a hybrid epithelial/mesenchymal phenotype by upregulating both E-cadherin and ZEB, and correlates this phenotype with poor survival in cancer.

Towards understanding cancer stem cell heterogeneity in the tumor microenvironment

This paper develops a computational-experimental framework to explain the spatial heterogeneity of cancer stem cells in the tumor microenvironment, showing that Notch-JAG1 signaling and inflammatory cytokines drive CSC distribution and stemness.

A mechanism-based computational model to capture the interconnections among epithelial-mesenchymal transition, cancer stem cells and Notch-Jagged signaling

The paper develops a computational model to explore the interactions between EMT, CSCs, and Notch-Jagged signaling, revealing how hybrid E/M cells with stemness traits and enhanced Notch-Jagged signaling contribute to therapeutic resistance.

PAGE4 and Conformational Switching: Insights from Molecular Dynamics Simulations and Implications for Prostate Cancer

This study uses molecular dynamics simulations to investigate how phosphorylation of PAGE4 affects its structure and interactions with AP-1 and AR, revealing conformational switching linked to prostate cancer progression.

Numb prevents a complete EMT by modulating Notch signalling

This study shows Numb stabilizes a hybrid E/M phenotype by inhibiting Notch-driven full EMT, correlates with poor cancer survival, and predicts its role in tumor-initiation.

De Novo Prediction of Human Chromosome Structures: Epigenetic Marking Patterns Encode Genome Architecture

The paper predicts human chromosome structures from epigenetic data, showing that chromatin architecture can be inferred through phase separation-like processes using ChIP-Seq and Hi-C data.

Distinguishing Mechanisms Underlying EMT Tristability

The paper uses experimental and theoretical approaches to evaluate two models of EMT dynamics, finding experimental evidence supporting the ternary chimera switch model over the cascading bistable switches model.