Protein Frustratometer 2: a tool to localize energetic frustration in protein molecules, now with electrostatics.
Nucleic Acids Research 44(W1):W356 (2016)
The protein frustratometer is an energy landscape theory-inspired algorithm that aims at localizing and quantifying the energetic frustration present in protein molecules. Frustration is a useful concept for analyzing proteins' biological behavior. It compares the energy distributions of the nat...
Exploring the Free Energy Landscape of Nucleosomes.
Journal of the American Chemical Society 138(26):8126 (2016)
The nucleosome is the fundamental unit for packaging the genome. A detailed molecular picture for its conformational dynamics is crucial for understanding transcription and gene regulation. We investigate the disassembly of single nucleosomes using a predictive coarse-grained protein DNA model w...
Shape Transitions and Chiral Symmetry Breaking in the Energy Landscape of the Mitotic Chromosome.
Physical Review Letters 116(24):248101 (2016)
We derive an unbiased information theoretic energy landscape for chromosomes at metaphase using a maximum entropy approach that accurately reproduces the details of the experimentally measured pairwise contact probabilities between genomic loci. Dynamical simulations using this landscape lead to...
Energy landscapes of a mechanical prion and their implications for the molecular mechanism of long-term memory.
PNAS 113(18):5006 (2016)
Aplysia cytoplasmic polyadenylation element binding (CPEB) protein, a translational regulator that recruits mRNAs and facilitates translation, has been shown to be a key component in the formation of long-term memory. Experimental data show that CPEB exists in at least a low-molecular weight coi...
Topological constraints and modular structure in the folding and functional motions of GlpG, an intramembrane protease.
PNAS 113(8):2098 (2016)
We investigate the folding of GlpG, an intramembrane protease, using perfectly funneled structure-based models that implicitly account for the absence or presence of the membrane. These two models are used to describe, respectively, folding in detergent micelles and folding within a bilayer, whi...
Binding of NFκB Appears to Twist the Ankyrin Repeat Domain of IκBα.
Biophysical Journal 110(4):887 (2016)
Total internal reflection fluorescence-based single-molecule Förster resonance energy transfer (FRET) measurements were previously carried out on the ankyrin repeat domain (ARD) of IκBα, the temporally regulated inhibitor of canonical NFκB signaling. Under native conditions, most of the IκBα mol...
Molecular stripping in the NF-κB/IκB/DNA genetic regulatory network.
PNAS 113(1):110 (2016)
Genetic switches based on the [Formula: see text] system are master regulators of an array of cellular responses. Recent kinetic experiments have shown that [Formula: see text] can actively remove NF-κB bound to its genetic sites via a process called "molecular stripping." This allows the [Formu...
Electrostatics, structure prediction, and the energy landscapes for protein folding and binding.
Protein Science 25(1):255 (2016)
While being long in range and therefore weakly specific, electrostatic interactions are able to modulate the stability and folding landscapes of some proteins. The relevance of electrostatic forces for steering the docking of proteins to each other is widely acknowledged, however, the role of el...
Predictive energy landscapes for folding membrane protein assemblies.
Journal of Chemical Physics 143(24):243101 (2015)
We study the energy landscapes for membrane protein oligomerization using the Associative memory, Water mediated, Structure and Energy Model with an implicit membrane potential (AWSEM-membrane), a coarse-grained molecular dynamics model previously optimized under the assumption that the energy l...
Evolution, energy landscapes and the paradoxes of protein folding.
Biochimie 119:218 (2015)
Protein folding has been viewed as a difficult problem of molecular self-organization. The search problem involved in folding however has been simplified through the evolution of folding energy landscapes that are funneled. The funnel hypothesis can be quantified using energy landscape theory ba...
Dichotomous noise models of gene switches.
Journal of Chemical Physics 143(19):195101 (2015)
Molecular noise in gene regulatory networks has two intrinsic components, one part being due to fluctuations caused by the birth and death of protein or mRNA molecules which are often present in small numbers and the other part arising from gene state switching, a single molecule event. Stochast...
On the hydrodynamics of swimming enzymes.
Journal of Chemical Physics 143(16):165101 (2015)
Several recent experiments suggest that rather generally the diffusion of enzymes may be augmented through their activity. We demonstrate that such swimming motility can emerge from the interplay between the enzyme energy landscape and the hydrodynamic coupling of the enzyme to its environment. ...
Water Mediated Interactions and the Protein Folding Phase Diagram in the Temperature-Pressure Plane.
Journal of Physical Chemistry B 119(34):11416 (2015)
The temperature-pressure behavior of two proteins, ubiquitin and λ-repressor, is explored using a realistically coarse-grained physicochemical model, the associative memory, water mediated, structure and energy model (AWSEM). The phase diagram across the temperature-pressure plane is obtained by...
Topology, structures, and energy landscapes of human chromosomes.
PNAS 112(19):6062 (2015)
Chromosome conformation capture experiments provide a rich set of data concerning the spatial organization of the genome. We use these data along with a maximum entropy approach to derive a least-biased effective energy landscape for the chromosome. Simulations of the ensemble of chromosome conf...
Frustration in biomolecules.
Quarterly Reviews of Biophysics 47(4):285 (2014)
Biomolecules are the prime information processing elements of living matter. Most of these inanimate systems are polymers that compute their own structures and dynamics using as input seemingly random character strings of their sequence, following which they coalesce and perform integrated cellu...
Coevolutionary information, protein folding landscapes, and the thermodynamics of natural selection.
PNAS 111(34):12408 (2014)
The energy landscape used by nature over evolutionary timescales to select protein sequences is essentially the same as the one that folds these sequences into functioning proteins, sometimes in microseconds. We show that genomic data, physical coarse-grained free energy functions, and family-sp...
Predictive energy landscapes for folding α-helical transmembrane proteins.
PNAS 111(30):11031 (2014)
We explore the hypothesis that the folding landscapes of membrane proteins are funneled once the proteins' topology within the membrane is established. We extend a protein folding model, the associative memory, water-mediated, structure, and energy model (AWSEM) by adding an implicit membrane po...
Dynamical heterogeneity of the glassy state.
Journal of Physical Chemistry B 118(28):7835 (2014)
We compare dynamical heterogeneities in equilibrated supercooled liquids and in the nonequilibrium glassy state within the framework of the random first order transition theory. Fluctuating mobility generation and transport in the glass are treated by numerically solving stochastic continuum equ...
Stem cell differentiation as a many-body problem.
PNAS 111(28):10185 (2014)
Stem cell differentiation has been viewed as coming from transitions between attractors on an epigenetic landscape that governs the dynamics of a regulatory network involving many genes. Rigorous definition of such a landscape is made possible by the realization that gene regulation is stochasti...
A second molecular biology revolution? The energy landscapes of biomolecular function.
Physical Chemistry Chemical Physics 16(14):6321 (2014)