A5071393850- RNA Research and Splicing
- Genomics and Chromatin Dynamics
- Protein Structure and Dynamics
- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- Lipid metabolism and biosynthesis
- Enzyme Structure and Function
- DNA and Nucleic Acid Chemistry
- Prion Diseases and Protein Misfolding
- Protein purification and stability
- Cellular Mechanics and Interactions
- Bacteriophages and microbial interactions
- Proteins in Food Systems
- Advanced biosensing and bioanalysis techniques
- Chromosomal and Genetic Variations
- Quantum, superfluid, helium dynamics
- nanoparticles nucleation surface interactions
- Molecular Junctions and Nanostructures
- Heat shock proteins research
- Spectroscopy and Quantum Chemical Studies
- Material Dynamics and Properties
- Force Microscopy Techniques and Applications
- Epigenetics and DNA Methylation
- Advanced Chemical Physics Studies
- Origins and Evolution of Life
University of Cambridge
2011-2025
Marine Biological Laboratory
2024
Princeton University
2023-2024
Universidad Complutense de Madrid
2024
Institute for Research in Biomedicine
2013-2015
Universitat Politècnica de Catalunya
2013-2015
New York University
2010-2013
Barcelona Supercomputing Center
2013
Universitat de Barcelona
2013
Courant Institute of Mathematical Sciences
2012
Abstract Liquid–liquid phase separation of proteins underpins the formation membraneless compartments in living cells. Elucidating molecular driving forces underlying protein transitions is therefore a key objective for understanding biological function and malfunction. Here we show that cellular proteins, which form condensates at low salt concentrations, including FUS, TDP-43, Brd4, Sox2, Annexin A11, can reenter phase-separated regime high concentrations. By bringing together experiments...
Significance LLPS plays an important role in the spatiotemporal organization of numerous molecular constituents living cells, via formation biomolecular condensates. Our simulations provide predictive rules governing stability and composition multicomponent Biomolecules that increase connectivity condensates are present higher concentrations because is positively correlated with stability. Greater within highly manifests critical temperatures phase diagrams accessible systems involving just...
Abstract Liquid–liquid phase separation (LLPS) is an important mechanism that helps explain the membraneless compartmentalization of nucleus. Because chromatin compaction and LLPS are collective phenomena, linking their modulation to physicochemical features nucleosomes challenging. Here, we develop advanced multiscale model—integrating atomistic representations, a chemically-specific coarse-grained model, minimal model—to resolve individual within sub-Mb domains phase-separated systems. To...
Liquid–liquid phase separation underlies the formation of biological condensates. Physically, such systems are microemulsions that in general have a propensity to fuse and coalesce; however, many condensates persist as independent droplets test tube inside cells. This stability is crucial for their function, but physicochemical mechanisms control emulsion remain poorly understood. Here, by combining single-condensate zeta potential measurements, optical microscopy, tweezer experiments,...
Phase-separated biomolecular condensates that contain multiple coexisting phases are widespread in vitro and cells. Multiphase emerge readily within multicomponent mixtures of biomolecules (e.g., proteins nucleic acids) when the different components present sufficient physicochemical diversity intermolecular forces, structure, chemical composition) to sustain separate phases. Because such is highly coupled solution conditions temperature, pH, salt, composition), it can manifest itself...
A wide range of macromolecules can undergo phase separation, forming biomolecular condensates in living cells. These membraneless organelles are typically highly dynamic, formed reversibly, and carry out essential functions biological systems. Crucially, however, a further liquid-to-solid transition the lead to irreversible pathological aggregation cellular dysfunction associated with onset development neurodegenerative diseases. Despite importance this proteins, mechanism by which it is...
Biomolecular condensates, compartments that concentrate molecules without surrounding membranes, are integral to numerous cellular processes. The structure and interaction networks of within condensates remain poorly understood. Using cryo-electron tomography molecular dynamics simulations we elucidated the phase separated chromatin across scales, from individual amino acids network architecture. We found internucleosomal DNA linker length controls nucleosome arrangement histone tail...
Biomolecular condensates composed of highly charged biomolecules, such as DNA, RNA, chromatin, and nucleic-acid binding proteins, are ubiquitous in the cell nucleus. The biophysical properties these charge-rich largely regulated by electrostatic interactions. Residue-resolution coarse-grained models that describe solvent ions implicitly widely used to gain mechanistic insights into condensates, offering transferability, computational efficiency, accurate predictions for multiple systems....
In a recent paper, we have developed an efficient implementation of the ring polymer molecular dynamics (RPMD) method for calculating bimolecular chemical reaction rates in gas phase, and illustrated it with applications to some benchmark atom–diatom reactions. this show that same methodology can readily be used treat more complex polyatomic reactions their full dimensionality, such as hydrogen abstraction from methane, H + \documentclass[12pt]{minimal}\begin{document}${\rm CH}_4...
Histone tails and their epigenetic modifications play crucial roles in gene expression regulation by altering the architecture of chromatin. However, structural mechanisms which histone influence interconversion between active inactive chromatin remain unknown. Given technical challenges obtaining detailed experimental characterizations structure chromatin, multiscale computations offer a promising alternative to model effect on folding. Here we combine multimicrosecond atomistic molecular...
Deciphering the factors that control chromatin fiber structure is key to understanding fundamental chromosomal processes. Although details remain unknown, it becoming clear polymorphic depending on internal and external factors. In particular, different lengths of linker DNAs joining successive nucleosomes (measured in nucleosome-repeat or NRLs) characterize cell types cycle stages produce structures. NRL also nonuniform within single fibers, but how this diversity affects not clear. Here we...
We describe an efficient procedure for calculating the rates of bimolecular chemical reactions in gas phase within ring polymer molecular dynamics approximation. A key feature is that it does not require one calculate absolute quantum mechanical partition function reactants or transition state: The rate coefficient only depends on ratio these two functions which can be obtained from a thermodynamic integration along suitable reaction coordinate. illustrated with applications to...
Biomolecular condensates, which assemble via the process of liquid–liquid phase separation (LLPS), are multicomponent compartments found ubiquitously inside cells. Experiments and simulations have shown that biomolecular condensates with many components can exhibit multilayered organizations. Using a minimal coarse-grained model for interacting multivalent proteins, we investigate thermodynamic parameters governing formation through changes in protein valency binding affinity. We focus on...
Abstract Biomolecular condensates, some of which are liquid-like during health, can age over time becoming gel-like pathological systems. One potential source loss properties ageing RNA-binding protein condensates is the progressive formation inter-protein β -sheets. To bridge microscopic understanding between accumulation -sheets and modulation FUS hnRNPA1 condensate viscoelasticity, we develop a multiscale simulation approach. Our method integrates atomistic simulations with...
Biomolecular condensates formed via liquid-liquid phase separation (LLPS) play a crucial role in the spatiotemporal organization of cell material. Nucleic acids can act as critical modulators stability these protein condensates. To unveil RNA length regulating binding (RBP) condensates, we present multiscale computational strategy that exploits advantages sequence-dependent coarse-grained representation proteins and minimal model wherein are described patchy colloids. We find for constant...
Biomolecular condensates are important contributors to the internal organization of cell material. While initially described as liquid-like droplets, term biomolecular is now used describe a diversity condensed phase assemblies with material properties extending from low high viscous liquids, gels, and even glasses. Because determined by intrinsic behavior their molecules, characterizing such integral rationalizing molecular mechanisms that dictate functions roles in health disease. Here, we...
We develop a computational method integrating genetic algorithm with residue-level coarse-grained model of intrinsically disordered proteins in order to uncover the molecular origins multiphase condensates and enable their controlled design.
Intracellular liquid–liquid phase separation (LLPS) of proteins and nucleic acids is a fundamental mechanism by which cells compartmentalize their components perform essential biological functions. Molecular simulations play crucial role in providing microscopic insights into the physicochemical processes driving this phenomenon. In study, we systematically compare six state-of-the-art sequence-dependent residue-resolution models to evaluate performance reproducing behaviour material...
We have used the ring polymer molecular dynamics method to study Azzouz-Borgis model for proton transfer between phenol (AH) and trimethylamine (B) in liquid methyl chloride. When A-H distance is as reaction coordinate, trajectories are found exhibit multiple recrossings of transition state dividing surface give a rate coefficient that smaller than quantum theory value by an order magnitude. This be expected on kinematic grounds heavy-light-heavy when light atom coordinate it clearly...