arXiv subjects

Jian-Min Yuan

Publications and source records attributed to Jian-Min Yuan.

8 recordsLinked to original sources

arXiv2022

Stochastic Kinetic Study of Protein Aggregation and Molecular Crowding Effects of Ab40 and Ab42

Two isoforms of beta amyloid peptides, Ab40 and Ab42, differ from each other only in the last two amino acids, IA, at the end of Ab42. They, however, differ significantly in their ability in inducing Alzheimer's disease (AD). The rate curves of fibril growth of Ab40 and Ab42 and the effects of molecular crowding have been measured in in vitro experiments. These experimental curves, on the other hand, have been fitted in terms of rate constants for elementary reaction steps using rate equation approaches. Several sets of such rate parameters have been reported in the literature. Employing a recently developed stochastic kinetic method, implemented in a browser-based simulator, popsim, we study to reveal the differences in the kinetic behaviors implied by these sets of rate parameters. In particular, the stochastic method is used to distinguish the kinetic behaviors between Ab40 and Ab42 isoforms. As a result, we make general comments on the usefulness of these sets of rate parameters.

physics.bio-ph↗

arXiv2021

Stochastic kinetic treatment of protein aggregation and the effects of macromolecular crowding

Investigation of protein self-assembly processes is important for the understanding of the growth processes of functional proteins as well as disease-causing amyloids. Inside cells, intrinsic molecular fluctuations are so high that they cast doubt on the validity of the deterministic rate equation approach. Furthermore, the protein environments inside cells are often crowded with other macromolecules, with volume fractions of the crowders as high as 40%. We study protein self-aggregation at the cellular level using Gillespie's stochastic algorithm and investigate the effects of macromolecular crowding using models built on scaled-particle and transition-state theories. The stochastic kinetic method can be formulated to provide information on the dominating aggregation mechanisms in a method called reaction frequency (or propensity) analysis. This method reveals that the change of scaling laws related to the lag time can be directly related to the change in the frequencies of reaction mechanisms. Further examination of the time evolution of the fibril mass and length quantities unveils that maximal fluctuations occur in the periods of rapid fibril growth and the fluctuations of both quantities can be sensitive functions of rate constants. The presence of crowders often amplifies the roles of primary and secondary nucleation and causes shifting in the relative importance of elongation, shrinking, fragmentation and coagulation of linear aggregates. Comparison of the results of stochastic simulations with those of rate equations gives us information on the convergence relation between them and how the roles of reaction mechanisms change as the system volume is varied.

physics.bio-ph↗

arXiv2013

A Kinetic Study of Amyloid Formation: Fibril Growth and Length Distributions

We propose a kinetic model for the self-aggregation by amyloid proteins. By extending several well-known models for protein aggregation, the time evolution of aggregate concentrations containing $r$ proteins, denoted $c_r(t)$, can be written in terms of generalized Smoluchowski kinetics. With this approach we take into account all possible aggregation and fragmentation reactions involving clusters of any size. Correspondingly, an aggregate of size x+y could be formed by or break-up into two smaller constituent aggregates of sizes x and y. The rates of each aggregation or fragmentation reaction, called kernels, are specified in terms of the aggregate size, and we solve $c_r(t)$ for large cluster sizes using numerical techniques. We show that by using Smoluchowski kinetics many pathways to fibrillation are possible and quantities, such as the aggregate length distribution at an arbitrary time, can be calculated. We show that the predicted results of the model are in agreement with the experimental observations.

physics.chem-ph↗

arXiv2013

Statistical Mechanical Treatments of Protein Amyloid Formation

Protein aggregation is an important field of investigation because it is closely related to the problem of neurodegenerative diseases, to the development of biomaterials, and to the growth of cellular structures such as cyto-skeleton. Self-aggregation of protein amyloids, for example, is a complicated process involving many species and levels of structures. This complexity, however, can be dealt with using statistical mechanical tools, such as free energies, partition functions, and transfer matrices. In this article, we review general strategies for studying protein aggregation using statistical mechanical approaches and show that canonical and grand canonical ensembles can be used in such approaches. The grand canonical approach is particularly convenient since competing pathways of assembly and dis-assembly can be considered simultaneously. Another advantage of using statistical mechanics is that numerically exact solutions can be obtained for all of the thermodynamic properties of fibrils, such as the amount of fibrils formed, as a function of initial protein concentration. Furthermore, statistical mechanics models can be used to fit experimental data when they are available for comparison.

cond-mat.stat-mech↗

arXiv2011

A Statistical Mechanical Approach to Protein Aggregation

We develop a theory of aggregation using statistical mechanical methods. An example of a complicated aggregation system with several levels of structures is peptide/protein self-assembly. The problem of protein aggregation is important for the understanding and treatment of neurodegenerative diseases and also for the development of bio-macromolecules as new materials. We write the effective Hamiltonian in terms of interaction energies between protein monomers, protein and solvent, as well as between protein filaments. The grand partition function can be expressed in terms of a Zimm-Bragg-like transfer matrix, which is calculated exactly and all thermodynamic properties can be obtained. We start with two-state and three-state descriptions of protein monomers using Potts models that can be generalized to include q-states, for which the exactly solvable feature of the model remains. We focus on n X N lattice systems, corresponding to the ordered structures observed in some real fibrils. We have obtained results on nucleation processes and phase diagrams, in which a protein property such as the sheet content of aggregates is expressed as a function of the number of proteins on the lattice and inter-protein or interfacial interaction energies. We have applied our methods to Aβ(1-40) and Curli fibrils and obtained results in good agreement with experiments.

q-bio.BM↗

arXiv2011

Exactly Solvable Model for Helix-Coil-Sheet Transitions in Protein Systems

In view of the important role helix-sheet transitions play in protein aggregation, we introduce a simple model to study secondary structural transitions of helix-coil-sheet systems using a Potts model starting with an effective Hamiltonian. This energy function depends on four parameters that approximately describe entropic and enthalpic contributions to the stability of a polypeptide in helical and sheet conformations. The sheet structures involve long-range interactions between residues which are far in sequence, but are in contact in real space. Such contacts are included in the Hamiltonian. Using standard statistical mechanical techniques, the partition function is solved exactly using transfer matrices. Based on this model, we study thermodynamic properties of polypeptides, including phase transitions between helix, sheet, and coil structures.

physics.bio-ph↗

arXiv2009

Experimental verification of statistical correlation for bosons: Another kind of Hong-Ou-Mandel interference

According to the identity principle in quantum theory, states of a system consisted of identical particles should maintain unchanged under interchanging between two of the particles. The whole wavefunction should be symmetrized or antisymmetrized. This leads to statistical correlations between particles, which exhibit observable effects. We design an experiment to directly observe such effects for bosons. The experiment is performed with two photons. The effect of statistical correlations is clearly observed when the wavepackets of two photons are completely overlapped, and this effect varies with the degree of overlapping. The results of our experiment substantiate the statistical correlation in a simple way. Experiment reported here can also be regarded as another kind of two-photon Hong-Ou-Mandel interference, occurs in the polarization degree of freedom of photon.

quant-ph↗

arXiv2001

Classical calculation of high-order harmonic generation of atomic and molecular gases in intense laser fields

Based upon our previous works (Eur.Phys.J.D 6, 319(1999); Chin.Phys.Lett. 18, 236(2001)), we develop a classical approach to calculate the high-order harmonic generation of the laser driven atoms and molecules. The Coulomb singularities in the system have been removed by a regularization procedure. Action-angle variables have been used to generate the initial microcanonical distribution which satisfies the inversion symmetry of the system. The numerical simulation show, within a proper laser intensity, a harmonic plateau with only odd harmonics appears. At higher intensities, the spectra become noisier because of the existence of chaos. With further increase in laser intensity, ionization takes place, and the high-order harmonics disappear. Thus chaos introduces noise in the spectra, and ionization suppresses the harmonic generation, with the onset of the ionization follows the onset of chaos.

physics.atom-ph↗