arXiv subjects

Mai Suan Li

Publications and source records attributed to Mai Suan Li.

At least 19 recordsLinked to original sources

arXiv2014

Measurements of Stationary Josephson Current between High-$T_{c}$ Oxides as a Tool to Detect Charge Density Waves

Stationary Josephson tunnel current $I_{c}$ between superconductors with $d$-wave order parameter symmetry and charge-density-wave (CDW) partial gapping was analyzed in the two-dimensional model appropriate to high-$T_{c}$ cuprates. It was shown that, in certain experimental setups, due to the peculiar overlap of superconducting and CDW gaps in the momentum space, the dependence of $I_{c}$ on the CDW parameters may be strongly nonmonotonic. Hence, we suggested that $I_{c}$ measurements in the wide range of dopings can serve as an indicator of CDW existence in the pseudogap regions of the cuprate phase diagrams. Besides, the orientation $I_{c}$-dependences were analyzed.

cond-mat.supr-con↗

arXiv2013

A structure-based model fails to probe the mechanical unfolding pathways of the titin I27 domain

We discuss the use of a structure based C$α$-Go model and Langevin dynamics to study in detail the mechanical properties and unfolding pathway of the titin I27 domain. We show that a simple Go-model does detect correctly the origin of the mechanical stability of this domain. The unfolding free energy landscape parameters $x_u$ and $ΔG^{\ddagger}$, extracted from dependencies of unfolding forces on pulling speeds, are found to agree reasonably well with experiments. We predict that above $v=10^4$ nm/s the additional force-induced intermediate state is populated at an end-to-end extension of about $75 \mathring{A}$. The force-induced switch in the unfolding pathway occurs at the critical pulling speed $v_{crit} \approx 10^6-10^7$ nm/s. We argue that this critical pulling speed is an upper limit of the interval where Bell's theory works. However, our results suggest that the Go-model fails to reproduce the experimentally observed mechanical unfolding pathway properly, yielding an incomplete picture of the free energy landscape. Surprisingly, the experimentally observed intermediate state with the A strand detached is not populated in Go-model simulations over a wide range of pulling speeds. The discrepancy between simulation and experiment is clearly seen from the early stage of the unfolding process which shows the limitation of the Go model in reproducing unfolding pathways and deciphering the complete picture of the free energy landscape.

physics.bio-ph↗

arXiv2012

Periodic force induced stabilization or destabilization of the denatured state of a protein

We have studied the effects of an external sinusoidal force in protein folding kinetics. The externally applied force field acts on the each amino acid residues of polypeptide chains. Our simulation results show that mean protein folding time first increases with driving frequency and then decreases passing through a maximum. With further increase of the driving frequency the mean folding time starts increasing as the noise-induced hoping event (from the denatured state to the native state) begins to experience many oscillations over the mean barrier crossing time period. Thus unlike one-dimensional barrier crossing problems, the external oscillating force field induces both \emph{stabilization or destabilization of the denatured state} of a protein. We have also studied the parametric dependence of the folding dynamics on temperature, viscosity, non-Markovian character of bath in presence of the external field.

physics.chem-ph↗

arXiv2012

Universal geometrical factor of protein conformations as a consequence of energy minimization

The biological activity and functional specificity of proteins depend on their native three-dimensional structures determined by inter- and intra-molecular interactions. In this paper, we investigate the geometrical factor of protein conformation as a consequence of energy minimization in protein folding. Folding simulations of 10 polypeptides with chain length ranging from 183 to 548 residues manifest that the dimensionless ratio (V/(A )) of the van der Waals volume V to the surface area A and average atomic radius of the folded structures, calculated with atomic radii setting used in SMMP [Eisenmenger F., et. al., Comput. Phys. Commun., 138 (2001) 192], approach 0.49 quickly during the course of energy minimization. A large scale analysis of protein structures show that the ratio for real and well-designed proteins is universal and equal to 0.491\pm0.005. The fractional composition of hydrophobic and hydrophilic residues does not affect the ratio substantially. The ratio also holds for intrinsically disordered proteins, while it ceases to be universal for polypeptides with bad folding properties.

physics.bio-ph↗

arXiv2010

Factors governing fibrillogenesis of polypeptide chains

Using lattice models we explore the factors that determine the tendencies of polypeptide chains to aggregate by exhaustively sampling the sequence and conformational space. The morphologies of the fibril-like structures and the time scales ($τ_{fib}$) for their formation depend on a balance between hydrophobic and coulomb interactions. The extent of population of an ensemble of \textbf{N$^*$} structures, which are fibril-prone structures in the spectrum of conformations of an isolated protein, is the major determinant of $τ_{fib}$. This observation is used to determine the aggregating sequences by exhaustively exploring the sequence space, thus providing a basis for genome wide search of fragments that are aggregation prone.

cond-mat.soft↗

arXiv2010

Determination of factors governing fibrillogenesis of polypeptide chains using lattice models

Using lattice models we explore the factors that determine the tendencies of polypeptide chains to aggregate by exhaustively sampling the sequence and conformational space. The morphologies of the fibril-like structures and the time scales ($τ_{fib}$) for their formation depend on a subtle balance between hydrophobic and coulomb interactions. The extent of population of a fibril-prone structure in the spectrum of monomer conformations is the major determinant of $τ_{fib}$. This observation is used to determine the aggregation-prone consensus sequences by exhaustively exploring the sequence space. Our results provide a basis for genome wide search of fragments that are aggregation prone.

q-bio.BM↗

arXiv2009

Dependence of protein mechanical unfolding pathways on pulling speeds

Mechanical unfolding of the fourth domain of Distyostelium discoideum filamin (DDFLN4) was studied in detail using the C$_α$-Go model. We show that unfolding pathways of this protein depend on the pulling speed. The agreement between theoretical and experimental results on the sequencing of unfolding events is achieved at low loading rates. The unfolding free energy landscape is also constructed using dependencies of unfolding forces on pulling speeds.

q-bio.BM↗

arXiv2009

Protein mechanical unfolding: importance of non-native interactions

Mechanical unfolding of the fourth domain of Distyostelium discoideum filamin (DDFLN4) was studied by all-atom molecular dynamics simulations, using the GROMOS96 force field 43a1 and the simple point charge explicit water solvent. Our study reveals an important role of non-native interactions in the unfolding process. Namely, the existence of a peak centered at the end-to-end extension 22 nm in the force-extension curve, is associated with breaking of non-native hydrogen bonds. Such a peak has been observed in experiments but not in Go models, where non-native interactions are neglected. We predict that an additional peak occurs at 2 nm using not only GROMOS96 force field 43a1 but also Amber 94 and OPLS force fields. This result would stimulate further experimental studies on elastic properties of DDFLN4.

q-bio.BM↗

arXiv2008

New method for deciphering free energy landscape of three-state proteins

We have developed a new simulation method to estimate the distance between the native state and the first transition state, and the distance between the intermediate state and the second transition state of a protein which mechanically unfolds via intermediates. Assuming that the end-to-end extension $ΔR$ is a good reaction coordinate to describe the free energy landscape of proteins subjected to an external force, we define the midpoint extension $ΔR^*$ between two transition states from either constant-force or constant loading rate pulling simulations. In the former case, $ΔR^*$ is defined as a middle point between two plateaus in the time-dependent curve of $ΔR$, while, in the latter one, it is a middle point between two peaks in the force-extension curve. Having determined $ΔR^*$, one can compute times needed to cross two transition state barriers starting from the native state. With the help of the Bell and microscopic kinetic theory, force dependencies of these unfolding times can be used to locate the intermediate state and to extract unfolding barriers. We have applied our method to the titin domain I27 and the fourth domain of {\em Dictyostelium discoideum} filamin (DDFLN4), and obtained reasonable agreement with experiments, using the C$_α$-Go model.

q-bio.BM↗

arXiv2008

Probing the Mechanisms of Fibril Formation Using Lattice Models

Using exhaustive Monte Carlo simulations we study the kinetics and mechanism of fibril formation using lattice models as a function of temperature and the number of chains. While these models are, at best, caricatures of peptides, we show that a number of generic features thought to govern fibril assembly are present in the toy model. The monomer, which contains eight beads made from three letters (hydrophobic, polar, and charged), adopts a compact conformation in the native state. The kinetics of fibril assembly occurs in three distinct stages. In each stage there is a cascade of events that transforms the monomers and oligomers to ordered structures. In the first "burst" stage highly mobile oligomers of varying sizes form. The conversion to the aggregation-prone conformation occurs within the oligomers during the second stage. As time progresses, a dominant cluster emerges that contains a majority of the chains. In the final stage, the aggregation-prone conformation particles serve as a template onto which smaller oligomers or monomers can dock and undergo conversion to fibril structures. The overall time for growth in the latter stages is well described by the Lifshitz-Slyazov growth kinetics for crystallization from super-saturated solutions.

q-bio.BM↗

arXiv2007

New force replica exchange method and protein folding pathways probed by force-clamp technique

We have developed a new extended replica exchange method to study thermodynamics of a system in the presence of external force. Our idea is based on the exchange between different force replicas to accelerate the equilibrium process. We have shown that the refolding pathways of single ubiquitin depend on which terminus is fixed. If the N-end is fixed then the folding pathways are different compared to the case when both termini are free, but fixing the C-terminal does not change them. Surprisingly, we have found that the anchoring terminal does not affect the pathways of individual secondary structures of three-domain ubiquitin, indicating the important role of the multi-domain construction. Therefore, force-clamp experiments, in which one end of a protein is kept fixed, can probe the refolding pathways of a single free-end ubiquitin if one uses either the poly-ubiquitin or a single domain with the C-terminus anchored. However, it is shown that anchoring one end does not affect refolding pathways of the titin domain I27, and the force-clamp spectroscopy is always capable to predict folding sequencing of this protein. We have obtained the reasonable estimate for unfolding barrier of ubiqutin. The linkage between residue Lys48 and the C-terminal of ubiquitin is found to have the dramatic effect on the location of the transition state along the end-to-end distance reaction coordinate, but the multi-domain construction leaves the transition state almost unchanged. We have found that the maximum force in the force-extension profile from constant velocity force pulling simulations depends on temperature nonlinearly. However, for some narrow temperature interval this dependence becomes linear, as have been observed in recent experiments.

q-bio.BM↗

arXiv2006

Effect of finite size on cooperativity and rates of protein folding

We analyze the dependence of cooperativity of the thermal denaturation transition and folding rates of globular proteins on the number of amino acid residues, $N$, using lattice models with side chains,off-lattice Go models and the available experimental data. A dimensionless measure of cooperativity, $Ω_c$ ($0 < Ω_c < \infty$), scales as $Ω_c \sim N^ζ$. The results of simulations and the analysis of experimental data further confirm the earlier prediction that $ζ$ is universal with $ζ= 1 +γ$, where exponent $γ$ characterizes the susceptibility of a self-avoiding walk. This finding suggests that the structural characteristics in the denaturated state are manifested in the folding cooperativity at the transition temperature. The folding rates $k_F$ for the Go models and a dataset of 69 proteins can be fit using $k_F = k_F^0 \exp(-cN^β)$. Both $β= 1/2$ and 2/3 provide a good fit of the data. We find that $k_F = k_F^0 \exp(-cN^{1/2})$, with the average (over the dataset of proteins) $k_F^0 \approx (0.2μs)^{-1}$ and $c \approx 1.1$, can be used to estimate folding rates to within an order of magnitude in most cases. The minimal models give identical $N$ dependence with $c \approx 1$. The prefactor for off-lattice Go models is nearly four orders of magnitude larger than the experimental value.

q-bio.BM↗

arXiv2006

Folding of the Protein Domain hbSBD

The folding of the alpha-helice domain hbSBD of the mammalian mitochondrial branched-chain alpha-ketoacid dehydrogenase (BCKD) complex is studied by the circular dichroism technique in absence of urea. Thermal denaturation is used to evaluate various thermodynamic parameters defining the equilibrium unfolding, which is well described by the two-state model with the folding temperature T_f = 317.8 K and the enthalpy change Delta H_g = 19.67 kcal/mol. The folding is also studied numerically using the off-lattice coarse-grained Go model and the Langevin dynamics. The obtained results, including the population of the native basin, the free energy landscape as a function of the number of native contacts and the folding kinetics, also suggest that the hbSBD domain is a two-state folder. These results are consistent with the biological function of hbSBD in BCKD.

q-bio.BM↗

arXiv2006

Refolding upon force quench and pathways of mechanical and thermal unfolding of ubiquitin

The refolding from stretched initial conformations of ubiquitin (PDB ID: 1ubq) under the quenched force is studied using the Go model and the Langevin dynamics. It is shown that the refolding decouples the collapse and folding kinetics. The force quench refolding times scale as tau_F ~ exp(f_q*x_F/k_B*T), where f_q is the quench force and x_F = 0.96 nm is the location of the average transition state along the reaction coordinate given by the end-to-end distance. This value is close to x_F = 0.8 nm obtained from the force-clamp experiments. The mechanical and thermal unfolding pathways are studied and compared with the experimental and all-atom simulation results in detail. The sequencing of thermal unfolding was found to be markedly different from the mechanical one. It is found that fixing the N-terminus of ubiquitin changes its mechanical unfolding pathways much more drastically compared to the case when the C-end is anchored. We obtained the distance between the native state and the transition state x_UF=0.24 nm which is in reasonable agreement with the experimental data.

q-bio.BM↗

arXiv2004

Finite size effects on calorimetric cooperativity of two-state proteins

Finite size effects on the calorimetric cooperatity of the folding-unfolding transition in two-state proteins are considered using the Go lattice models with and without side chains. We show that for models without side chains a dimensionless measure of calorimetric cooperativity kappa2 defined as the ratio of the van't Hoff to calorimetric enthalpy does not depend on the number of amino acids N. The average value of kappa2 is about 3/4 which is lower than the experimental value kappa2=1. For models with side chains kappa2 approaches unity as kappa2 \sim N^mu, where exponent mu=0.17. Above the critical chain length Nc =135 these models can mimic the truly all-or-non folding-unfolding transition.

q-bio.BM↗

arXiv2004

Finite size effects on thermal denaturation of globular proteins

Finite size effects on the cooperative thermal denaturation of proteins are considered. A dimensionless measure of cooperativity, Omega, scales as N^zeta, where N is the number of amino acids. Surprisingly, we find that zeta is universal with zeta = 1 + gamma, where the exponent gamma characterizes the divergence of the susceptibility for a self-avoiding walk. Our lattice model simulations and experimental data are consistent with the theory. Our finding rationalizes the marginal stability of proteins and substantiates the earlier predictions that the efficient folding of two-state proteins requires the folding transition temperature to be close to the collapse temperature.

q-bio.BM↗

arXiv2004

1/f Noise in a one-dimensional charge density wave system

The current noise in a classical one-dimensional charge density wave system is studied in the weak pinning regime by solving the overdamped equation of motion numerically. At low temperatures and just above the zero temperature depinning threshold, the power spectrum of the current noise $S(f)$ was found to scale with frequency $f$ as $S(f) \sim f^{-γ}$, where $γ\approx 1$, suggesting the existence of {\it flicker noise}. Our result is in agreement with experimental findings for quasi-one-dimensional charge density wave systems and provides the first evidence of $1/f$ behavior obtained from first principles.

cond-mat.dis-nn↗

arXiv2003

Thermal denaturation and folding rates of single domain proteins: size matters

We analyze the dependence of thermal denaturation transition and folding rates of globular proteins on the number of amino acid residues, N. Using lattice Go models we show that DeltaT/T_F ~ N^-1, where T_F is the folding transition temperature and DeltaT is the folding transition width. This finding is consistent with finite size effects expected for the systems undergoing a phase transition from a disordered to an ordered phase. The dependence of the folding rates k_F on N for lattice models and the dataset of 57 proteins and peptides shows that k_F = k_F^0 exp(-CN^beta) provides a good fit, if 0 < beta <= 2/3 and C is a constant. We find that k_F = k_F^0 exp(-1.1N^0.5) with k_F^0 =(0.4x10^-6 s)^-1 can estimate optimal protein folding rates to within an order of magnitude in most cases. By using this fit for a set of proteins with beta-sheet topology we find that k_F^0 is approximately equal to k_U^0, the prefactor for unfolding rates. The maximum ratio of k_U^0/k_F^0 is 10 for this class of proteins.

q-bio.BM↗