arXiv subjects

Trinh Xuan Hoang

Publications and source records attributed to Trinh Xuan Hoang.

At least 19 recordsLinked to original sources

arXiv2025

The protein escape process at the ribosomal exit tunnel has conserved mechanisms across the domains of life

The ribosomal exit tunnel is the primary structure affecting the release of nascent proteins at the ribosome. The ribosomal exit tunnels from different species have elements of conservation and differentiation in structural and physico-chemical properties. In this study, by simulating the elongation and escape processes of nascent proteins at the ribosomal exit tunnels of four different organisms, we show that the escape process has conserved mechanisms across the domains of life. Specifically, it is found that the escape process of proteins follows the diffusion mechanism given by a simple diffusion model and the median escape time positively correlates with the number of hydrophobic residues and the net charge of a protein for all the exit tunnels considered. These properties hold for twelve distinct proteins considered in two slightly different and improved Gō-like models. It is also found that the differences in physico-chemical properties of the tunnels lead to quantitative differences in the protein escape times. In particular, the relatively strong hydrophobicity of the E. coli's tunnel and the unusually high number of negatively charged amino acids on the tunnel's surface of H. marismortui lead to substantially slower escapes of proteins at these tunnels than at those of S. cerevisisae and H. sapiens.

cond-mat.soft↗

arXiv2025

Solvation enhances folding cooperativity and the topology dependence of folding rates in a lattice protein model

The aqueous solvent profoundly influences protein folding, yet its effects are relatively poorly understood. In this study, we investigate the impact of solvation on the folding of lattice proteins by using Monte Carlo simulations. The proteins are modelled as self-avoiding 27-mer chains on a cubic lattice, with compact native states and structure-based Gō potentials. Each residue that makes no contacts with other residues in a given protein conformation is assigned a solvation energy ε_s , representing its full exposure to the solvent. We find that a negative ε_s , indicating a favorable solvation, increases the cooperativity of the folding transition by lowering the free energy of the unfolded state, increasing the folding free energy barrier, and narrowing the folding routes. This favorable solvation also significantly improves the correlation between folding rates and the native topology, measured by the relative contact order. Our results suggest that Gō model may overestimate the importance of native interactions and a solvation potential countering the native bias can play a significant role. The solvation energy in our model can be related to the polar interaction between water and peptide groups in the protein backbone. It is therefore suggested that the solvation of peptide groups may significantly contribute to the exceptional folding cooperativity and the pronounced topology-dependence of folding rates observed in two-state proteins.

cond-mat.soft↗

arXiv2021

Proteins -- a celebration of consilience

Proteins are the common constituents of all living cells. They are molecular machines that interact with each other as well as with other cell products and carry out a dizzying array of functions with distinction. These interactions follow from their native state structures and therefore understanding sequence-structure relationships is of fundamental importance. What is quite remarkable about proteins is that their understanding necessarily straddles several disciplines. The importance of geometry in defining protein native state structure, the constraints placed on protein behavior by mathematics and physics, the need for proteins to obey the laws of quantum chemistry, and the rich role of evolution and biology all come together in defining protein science. Here we review ideas from the literature and present an interdisciplinary framework that aims to marry ideas from Plato and Darwin and demonstrates an astonishing consilience between disciplines in describing proteins. We discuss the consequences of this framework on protein behavior.

q-bio.BM↗

arXiv2021

Marginally compact phase and ordered ground states in a model polymer with side spheres

We present the results of a quantitative study of the phase behavior of a model polymer chain with side spheres using two independent computer simulation techniques. We find that the mere addition of side spheres results in key modifications of standard polymer behavior. One obtains a novel marginally compact phase at low temperatures, the structures in this phase are reduced in dimensionality and are ordered, they include strands assembled into sheets and a variety of helices, and at least one of the transitions on lowering the temperature to access these ordered states is found to be first order. Our model serves to partially bridge conventional polymer phases with biomolecular phases.

cond-mat.soft↗

arXiv2021

Spontaneous dimensional reduction and novel ground state degeneracy in a simple chain model

Chain molecules play a key role in the polymer field and in living cells. Our focus is on a new homopolymer model of a linear chain molecule subject to an attractive self-interaction promoting compactness. We analyze the model using simple analytic arguments complemented by extensive computer simulations. We find several striking results: there is a first order transition from a high temperature random coil phase to a highly unusual low temperature phase; the modular ground states exhibit significant degeneracy; the ground state structures exhibit spontaneous dimensional reduction and have a two-layer structure; and the ground states are assembled from secondary motifs of helices and strands connected by tight loops. We discuss the similarities and notable differences between the ground state structures (we call these PoSSuM -- Planar Structures with Secondary Motifs) in the novel phase and protein native state structures.

cond-mat.stat-mech↗

arXiv2020

Protein escape at the ribosomal exit tunnel: Effect of the tunnel shape

We study the post-translational escape of nascent proteins at the ribosomal exit tunnel with the consideration of a real shape atomistic tunnel based on the Protein Data Bank (PDB) structure of the large ribosome subunit of archeon Haloarcula marismortui. Molecular dynamics simulations employing the Go-like model for the proteins show that at intermediate and high temperatures, including a presumable physiological temperature, the protein escape process at the atomistic tunnel is quantitatively similar to that at a cylinder tunnel of length L = 72 Å and diameter d = 16 Å. At low temperatures, the atomistic tunnel, however, yields an increased probability of protein trapping inside the tunnel while the cylinder tunnel does not cause the trapping. All-$β$ proteins tend to escape faster than all-$α$ proteins but this difference is blurred on increasing the protein's chain length. A 29-residue zinc-finger domain is shown to be severely trapped inside the tunnel. Most of the single-domain proteins considered, however, can escape efficiently at the physiological temperature with the escape time distribution following the diffusion model proposed in our previous works. An extrapolation of the simulation data to a realistic value of the friction coefficient for amino acids indicates that the escape times of globular proteins are at the sub-millisecond scale. It is argued that this time scale is short enough for the smooth functioning of the ribosome by not allowing nascent proteins to jam the ribosome tunnel.

q-bio.BM↗

arXiv2018

Protein escape at the ribosomal exit tunnel: Effects of native interactions, tunnel length and macromolecular crowding

How fast a post-translational nascent protein escapes from the ribosomal exit tunnel is relevant to its folding and protection against aggregation. Here, by using Langevin molecular dynamics, we show that non-local native interactions help decreasing the escape time, and foldable proteins generally escape much faster than same-length self-repulsive homopolymers at low temperatures. The escape process, however, is slowed down by the local interactions that stabilize the α-helices. The escape time is found to increase with both the tunnel length and the concentration of macromolecular crowders outside the tunnel. We show that a simple diffusion model described by the Smoluchowski equation with an effective linear potential can be used to map out the escape time distribution for various tunnel lengths and various crowder concentrations. The consistency between the simulation data and the diffusion model however is found only for the tunnel length smaller than a cross-over length of 90 Å to 110 Å, above which the escape time increases much faster with the tunnel length. It is suggested that the length of ribosomal exit tunnel has been selected by evolution to facilitate both the efficient folding and efficient escape of single domain proteins. We show that macromolecular crowders lead to an increase of the escape time, and attractive crowders are unfavorable for the folding of nascent polypeptide.

q-bio.BM↗

arXiv2016

From polymers to proteins: effect of side chains and broken symmetry in the formation of secondary structures within a Wang-Landau approach

We study the equilibrium properties of a single flexible homopolymers where consecutive monomers are represented by impenetrable hard spherical beads tangential to each other, and non-consecutive monomers interact via a square-well potential. To this aim, we use both replica exchange canonical simulations and micro-canonical Wang-Landau techniques. We perform a close comparative analysis of the corresponding results, and find perfect agreement between the two methods as well as the past results. The model is then refined in two different directions. By allowing partial overlapping between consecutive beads, we break the spherical symmetry and thus provide a severe constraint on the possible conformations of the chain. This leads to a single helix or a double helix ground state, depending on the range of the interactions. Alternatively, we introduce additional spherical beads at specific positions to represent the steric hindrance of the side chains in real proteins. The ground state in this case is found to be again a globule, thus showing that contrary to some recent suggestions, side chains alone are not sufficient to insure a protein-like structure. Finally, we show that a combination of the above two effects increases the stability of the obtaining secondary structures, in agreement with previous results. The fundamental role played by the range of the square-well attraction is highlighted, and it is shown that they play a role similar to that found in simple liquids and polymers. Perspectives in terms of protein folding are finally discussed.

cond-mat.soft↗

arXiv2016

Folding and escape of nascent proteins at ribosomal exit tunnel

We investigate the interplay between post-translational folding and escape of two small single-domain proteins at the ribosomal exit tunnel by using Langevin dynamics with coarse-grained models. It is shown that at temperatures lower or near the temperature of the fastest folding, folding proceeds concomitantly with the escape process, resulting in vectorial folding and enhancement of foldability of nascent proteins. The concomitance between the two processes, however, deteriorates as temperature increases. Our folding simulations as well as free energy calculation by using umbrella sampling show that, at low temperatures, folding at the tunnel follows one or two specific pathways without kinetic traps. It is shown that the escape time can be mapped to a one-dimensional diffusion model with two different regimes for temperatures above and below the folding transition temperature. Attractive interactions between amino acids and attractive sites on the tunnel wall lead to a free energy barrier along the escape route of protein. It is suggested that this barrier slows down the escape process and consequently promotes correct folding of the released nascent protein.

q-bio.BM↗

arXiv2016

Transport properties through graphene grain boundaries: strain effects versus lattice symmetry

As most materials available in macroscopic quantities, graphene appears in a polycrystalline form and thus contains grain boundaries. In the present work, the effect of uniaxial strain on the electronic transport properties through graphene grain boundaries is investigated using atomistic simulations. A systematic picture of the transport properties with respect to the strain and the lattice symmetry of graphene domains on both sides of the boundary is provided. In particular, it is shown that the strain engineering can be used to open a finite transport gap in all graphene systems where two domains exhibit different orientations. This gap value is found to depend on the strain magnitude, on the strain direction and on the lattice symmetry of graphene domains. By choosing appropriately the strain direction, a large transport gap of a few hundred meV can be achieved when applying a small strain of only a few percents. For a specific class of graphene grain boundary systems, the strain engineering can also be used to reduce the scattering on defects and hence to significantly enhance the conductance. With a large strain-induced gap, these graphene heterostructures are proposed to be possible candidates for highly sensitive strain sensors, flexible transistors and p-n junctions with a strong non-linear I-V characteristics.

cond-mat.mes-hall↗

arXiv2014

From toroidal to rod-like condensates of semiflexible polymers

The competition between toroidal and rod-like conformations as possible ground states for DNA condensation is studied as a function of the stiffness, the length of the DNA and the form of the long-range interactions between neighboring molecules, using analytical theory supported by Monte Carlo simulations. Both conformations considered are characterized by a local nematic order with hexagonal packing symmetry of neighboring DNA molecules, but differ in global configuration of the chain and the distribution of its curvature as it wraps around to form a condensate. The long-range interactions driving the DNA condensation are assumed to be of the form pertaining to the attractive depletion potential as well as the attractive counterion induced soft potential. In the stiffness-length plane we find a transition between rod-like to toroid condensate for increasing stiffness at a fixed chain length $L$. Strikingly, the transition line is found to have a $L^{1/3}$ dependence irrespective of the details of the long-range interactions between neighboring molecules. When realistic DNA parameters are used, our description reproduces rather well some of the experimental features observed in DNA condensates.

cond-mat.soft↗

arXiv2012

Coil-globule transition of a homopolymer chain in a square-well potential: Comparison between Monte Carlo canonical replica exchange and Wang-Landau sampling

We study the equilibrium properties of a flexible homopolymer where consecutive monomers are represented by impenetrable hard spheres that are tangent to each other, and non-consecutive monomers interact via a square-well potential. To this aim, we use both replica exchange canonical simulations and micro-canonical Wang-Landau techniques for relatively short chains, and perform a close comparative analysis of the corresponding results. These investigations are then further exploited to reproduce, at a much shorter scale and, hence, computational effort, the phase diagram previously studied with much longer chains. This opens up the possibility of improving the model and introduce specificities typical, among other examples, of protein folding.

cond-mat.soft↗

arXiv2009

First-principles design of nanomachines

Learning from nature's amazing molecular machines, globular proteins, we present a framework for the predictive design of nano-machines. We show that the crucial ingredients for a chain molecule to behave as a machine are its inherent anisotropy and the coupling between the local Frenet coordinate reference frames of nearby monomers. We demonstrate that, even in the absence of heterogeneity, protein-like behavior is obtained for a simple chain molecule made up of just thirty hard spheres. This chain spontaneously switches between two distinct geometries, a single helix and a dual helix, merely due to thermal fluctuations.

cond-mat.soft↗

arXiv2005

Proteins and polymers

Proteins, chain molecules of amino acids, behave in ways which are similar to each other yet quite distinct from standard compact polymers. We demonstrate that the Flory theorem, derived for polymer melts, holds for compact protein native state structures and is not incompatible with the existence of structured building blocks such as $α$-helices and $β$-strands. We present a discussion on how the notion of the thickness of a polymer chain, besides being useful in describing a chain molecule in the continuum limit, plays a vital role in interpolating between conventional polymer physics and the phase of matter associated with protein structures.

q-bio.BM↗

arXiv2004

Mechanical properties of the domains of titin in a Go-like model

Comparison of properties of three domains of titin, I1, I27 and I28, in a simple geometry-based model shows that despite a high structural homology between their native states different domains show similar but distinguishable mechanical properties. Folding properties of the separate domains are predicted to be diversified which reflects sensitivity of the kinetics to the details of native structures. The Go-like model corresponding to the experimentally resolved native structure of the I1 domain is found to provide the biggest thermodynamic and mechanical stability compared to the other domains studied here. We analyze elastic, thermodynamic and kinetic properties of several structures corresponding to the I28 domain as obtained through homology-based modeling. We discuss the ability of the models of the I28 domain to reproduce experimental results qualitatively. A strengthening of contacts that involve hydrophobic amino acids does not affect theoretical comparisons of the domains. Tandem linkages of up to five identical or different domains unravel in a serial fashion at low temperatures. We study the nature of the intermediate state that arises in the early stages of the serial unraveling and find it to qualitatively agree with the results of Marszalek et al.

q-bio.BM↗

arXiv2004

Unified perspective on proteins: A physics approach

We study a physical system which, while devoid of the complexity one usually associates with proteins, nevertheless displays a remarkable array of protein-like properties. The constructive hypothesis that this striking resemblance is not accidental leads not only to a unified framework for understanding protein folding, amyloid formation and protein interactions but also has implications for natural selection.

cond-mat.stat-mech↗

arXiv2004

Geometry and symmetry presculpt the free-energy landscape of proteins

We present a simple physical model which demonstrates that the native state folds of proteins can emerge on the basis of considerations of geometry and symmetry. We show that the inherent anisotropy of a chain molecule, the geometrical and energetic constraints placed by the hydrogen bonds and sterics, and hydrophobicity are sufficient to yield a free energy landscape with broad minima even for a homopolymer. These minima correspond to marginally compact structures comprising the menu of folds that proteins choose from to house their native-states in. Our results provide a general framework for understanding the common characteristics of globular proteins.

q-bio.BM↗

arXiv2003

Thermal effects in stretching of Go-like models of titin and secondary structures

The effect of temperature on mechanical unfolding of proteins is studied using a Go-like model with a realistic contact map and Lennard-Jones contact interactions. The behavior of the I27 domain of titin and its serial repeats is contrasted to that of simple secondary structures. In all cases thermal fluctuations accelerate the unraveling process, decreasing the unfolding force nearly linearly at low temperatures. However differences in bonding geometry lead to different sensitivity to temperature and different changes in the unfolding pattern. Due to its special native state geometry titin is much more thermally and elastically stable than the secondary structures. At low temperatures serial repeats of titin show a parallel unfolding of all domains to an intermediate state, followed by serial unfolding of the domains. At high temperatures all domains unfold simultaneously and the unfolding distance decreases monotonically with the contact order, that is the sequence distance between the amino acids that form the native contact.

q-bio.BM↗