J. Mittal

Transient interdomain interactions modulate the monomeric structural ensemble and self-assembly of Huntingtin Exon 1

This study uses molecular dynamics simulations to show that transient interdomain interactions in Httex1 modulate its structural ensemble and self-assembly, contributing to aggregation in Huntington's disease.

Uncovering the molecular interactions underlying MBD2 and MBD3 phase separation

This study investigates the molecular interactions driving phase separation in MBD2 and MBD3 proteins, revealing distinct mechanisms despite their structural similarity.

RNA-binding tunes the conformational plasticity and intradomain stability of TDP-43 tandem RNA recognition motifs

This study uses molecular dynamics simulations to show RNA-binding stabilizes TDP-43 tandem RRMs and reduces conformational plasticity, preventing pathological aggregation.

Expanding the molecular grammar of polar residues and arginine in FUS prion-like domain phase separation and aggregation

The paper expands the molecular grammar of polar residues and arginine in FUS prion-like domain phase separation and aggregation by showing additional residues contribute to these processes.

Intra-condensate demixing of TDP-43 inside stress granules generates pathological aggregates

This study shows that TDP-43 aggregation in stress granules requires up-concentration and oxidative stress, leading to intra-condensate demixing and pathological aggregates.

Sequence-Dependent Conformational Transitions of Disordered Proteins During Condensation

This study investigates how sequence patterns in intrinsically disordered proteins affect their conformational transitions during condensation using a polyampholyte model.

Insights into Molecular Diversity within the FET Family: Unraveling Phase Separation of the N-Terminal Low Complexity Domain from RNA-Binding Protein EWS

This study investigates the phase separation mechanism of the EWSLCD domain using biophysical methods, revealing tyrosine residues as key drivers of condensate formation.

How a disordered linker in the Polycomb protein Polyhomeotic tunes phase separation and oligomerization

The paper investigates how a disordered linker in the Polyhomeotic protein influences phase separation and oligomerization in Drosophila and human cells through in vitro reconstitution and molecular dynamics simulations.

Conformational Properties of Polymers at Droplet Interfaces as Model Systems for Disordered Proteins

The paper uses polymer models to study conformational properties at droplet interfaces, finding compact conformations and segmental enrichment at the interface, which mirrors behavior in natural proteins.

Interplay between charge distribution and DNA in shaping HP1 paralog phase separation and localization

This study investigates how charge distribution and DNA influence the phase separation and localization of HP1 paralogs using simulations.

A coarse-grained DNA model to study protein-DNA interactions and liquid-liquid phase separation

This paper introduces a coarse-grained DNA model compatible with existing protein models to study protein-DNA interactions and liquid-liquid phase separation.

Sequence-Dependent Material Properties of Biomolecular Condensates and their Relation to Dilute Phase Conformations

This study computationally examines how sequence composition of charged disordered proteins affects their condensate material properties and finds similar responses to charge segregation across different sequences.

Determinants of Disordered Protein Co-Assembly Into Discrete Condensed Phases

The paper identifies sequence determinants of IDR co-assembly into distinct condensed phases and reveals physicochemical principles governing phase separation specificity.

Expanding the molecular language of protein liquid-liquid phase separation

This study explores how amino acid sequences influence protein liquid-liquid phase separation and material properties of condensates through systematic sequence manipulations and molecular simulations.

Role of Strong Localized vs. Weak Distributed Interactions in Disordered Protein Phase Separation

This study compares phase separation in intrinsically disordered proteins using two models with different interaction strengths and distributions, finding that distributed interactions promote liquid-like condensates over a broader range of compositions.

Aliphatic residues contribute significantly to the phase separation of TDP-43 C-terminal domain

This study identifies aliphatic residues as critical contributors to TDP-43 C-terminal domain phase separation, expanding the molecular understanding of protein phase separation.

Effect of Charge Distribution on the Dynamics of Polyampholytic Disordered Proteins

This study examines how charge distribution affects the dynamics of polyampholytic disordered proteins in dilute solutions, showing conformational and dynamic changes with increasing charge segregation.

Molecular interactions underlying the phase separation of HP1: Role of phosphorylation, ligand and nucleic acid binding

This study investigates how phosphorylation, ligand, and nucleic acid binding influence HP1's phase separation, revealing electrostatic interactions and conformational changes in its LLPS behavior.

Molecular insights into the effect of hexanediol on FUS phase separation

This study investigates how alkanediols, particularly 1,6-hexanediol, disrupt FUS phase separation using multiple techniques and identifies factors like geometry and hydrophobicity that influence their effectiveness.

Zn-dependent structural transition of SOD1 modulates its ability to undergo liquid-liquid phase separation.

This study shows that Zn-dependent structural changes in SOD1 affect its ability to undergo liquid-liquid phase separation, which may contribute to ALS pathology.

Amphiphilic proteins coassemble into multiphasic condensates and act as biomolecular surfactants

The paper investigates how amphiphilic proteins influence the structure and size of biomolecular condensates by forming surface layers and multiphasic structures.

A predictive coarse-grained model for position-specific effects of post-translational modifications on disordered protein phase separation

This paper develops a coarse-grained model to predict how position-specific post-translational modifications affect disordered protein phase separation.

Molecular details of protein condensates probed by microsecond-long atomistic simulations

The paper uses all-atom simulations to study protein condensates, revealing structural and dynamic details of phase separation in two IDPs and showing agreement with experiments.

Tyrosine phosphorylation regulates hnRNPA2 granule protein partitioning & reduces neurodegeneration

The paper shows tyrosine phosphorylation of hnRNPA2 reduces granule component partitioning and neurodegeneration in a C. elegans model.

Hydropathy patterning complements charge patterning to describe conformational preferences of disordered proteins

The paper introduces a new order parameter, SHD, and combines it with charge patterning to predict the scaling behavior of intrinsically disordered proteins from their sequences.

Identifying Sequence Perturbations to an Intrinsically Disordered Protein that Determine Its Phase Separation Behavior

This study identifies sequence features of an intrinsically disordered protein that influence its phase separation behavior through computational modeling and experimental validation.

TDP-43 α-helical structure tunes liquid-liquid phase separation and function

This study shows that mutations in TDP-43's helical region modulate its phase separation and function, with implications for ALS and synthetic biology.

Computational modeling highlights disordered Formin Homology 1 domain’s role in profilin-actin transfer

The paper uses simulations to show FH1 domains facilitate profilin-actin transfer, with flexibility and proximity to FH2 affecting efficiency.

Sequence determinants of protein phase behavior from a coarse-grained model

This paper develops a coarse-grained computational model to simulate liquid-liquid phase separation of proteins, showing it can capture phase diagram changes due to mutations and domain presence.

A Carbon Nanotube Optical Reporter Maps Endolysosomal Lipid Flux

This paper develops an optical reporter using carbon nanotubes to measure endolysosomal lipid flux in live cells, revealing lipid accumulation in disease models and sub-cellular heterogeneity.