How dynamic surface restructuring impacts intra-particle catalytic cooperativity.

Recent experiments indicated that nanoparticles (NPs) might efficiently catalyze multiple chemical reactions, frequently exhibiting new phenomena. One of those surprising observations is intra-particle catalytic cooperativity, when the reactions at one active site can stimulate the reactions at spatially distant sites. Theoretical explanations of these phenomena have been presented, pointing out the important role of charged hole dynamics.

Stochastic dynamics of hairballs in single-polymer growth.

Real-time monitoring of the single-chain growth of synthetic polymers shows that their end-to-end extension during polymerization in living conditions does not increase continuously. Instead, it remains in a non-equilibrium state, exhibiting stochastic wait-and-jump events when one end of the polymer is subjected to a constant force and the other end is clamped. This wait-and-jump observation was attributed to the stochastic formation and unwinding of conformational entanglements, referred to as hairballs, which result from intrachain and non-bonded interactions within the polymer.

Multivalent Salt-Induced Self-Assembly of Amphiphilic Polyelectrolytes of Different Charge Fractions: A Coarse-Grained Molecular Dynamics Simulation Study.

Amphiphilic polymers with both hydrophobic and hydrophilic blocks are of great interest for their potential applications in drug delivery. Their self-assembly behavior in response to environmental factors like ion charge and multivalent salt concentration has been the subject of recent investigation. Our study utilizes coarse-grained molecular dynamics simulations to investigate the aggregation behavior of amphiphilic copolymers upon introducing tetravalent salt at varying charge fractions.

Macromolecular Crowding Facilitates ssDNA Capture within Biological Nanopores: Role of Size Variation and Solution Heterogeneity.

Genetic sequencing is a vital process that requires the transport of charged nucleic acids through transmembrane nanopores. Single-molecule studies show that macromolecular bulk crowding facilitates the capture of these polymers, leading to a high throughput of nanopore sensors. Motivated by these observations, a minimal discrete-state stochastic framework was developed to describe the role of poly(ethylene glycol) (PEG) crowders in varying concentrations in the transport of ssDNA through α-hemolysin nanopores.

How Heterogeneity Affects Cooperative Communications within Single Nanocatalysts.

Catalysis remains one of the most essential methods in chemical research and industry. Recent experiments have discovered an unusual phenomenon of catalytic cooperativity, when a reaction at one active site can stimulate reactions at neighboring sites within single nanoparticles. While theoretical analysis established that the transport of charged holes is responsible for this phenomenon, it does not account for inhomogeneity in the structural and dynamic properties of single nanocatalysts.

Microscopic Mechanism of Macromolecular Crowder-Assisted DNA Capture and Translocation through Biological Nanopores.

Biological nanopore sensors are widely used for genetic sequencing as nucleic acids and other molecules translocate through them across membranes. Recent studies have shown that the transport of these polymers through nanopores is strongly influenced by macromolecular bulk crowders. By using poly(ethylene glycol) (PEG) molecules as crowders, experiments have shown an increase in the capture rates and translocation times of polymers through an α-hemolysin (αHL) nanopore, which provides high-throughput signals and accurate sensing.

Dynamics of chemical reactions on single nanocatalysts with heterogeneous active sites.

Modern chemical science and industries critically depend on the application of various catalytic methods. However, the underlying molecular mechanisms of these processes still remain not fully understood. Recent experimental advances that produced highly-efficient nanoparticle catalysts allowed researchers to obtain more quantitative descriptions, opening the way to clarify the microscopic picture of catalysis.

Theoretical Tools to Quantify Stochastic Fluctuations in Single-Molecule Catalysis by Enzymes and Nanoparticles.

Single-molecule microscopic techniques allow the counting of successive turnover events and the study of the time-dependent fluctuations of the catalytic activities of individual enzymes and different sites on a single heterogeneous nanocatalyst. It is important to establish theoretical methods to obtain the statistical measurements of such stochastic fluctuations that provide insight into the catalytic mechanism. In this review, we discuss a few theoretical frameworks for evaluating the first passage time distribution functions using a self-consistent pathway approach and chemical master equations, to establish a connection with experimental observables.

Theoretical insights into the full description of DNA target search by subdiffusing proteins.

DNA binding proteins (DBPs) diffuse in the cytoplasm to recognise and bind with their respective target sites on the DNA to initiate several biologically important processes. The first passage time distributions (FPTDs) of DBPs are useful in quantifying the timescales of the most-probable search paths in addition to the mean value of the distribution which, strikingly, are decades of order apart in time. However, extremely crowded conditions or the viscoelasticity of the cellular medium among other factors causes biomolecules to exhibit anomalous diffusion which is usually overlooked in most theoretical studies.

Coupling Effects of Electrostatic Interactions and Salt Concentration Gradient in Polymer Translocation through a Nanopore: A Coarse-Grained Molecular Dynamics Simulations Study.

We study the influence of polymer pore interactions and focus on the role played by the concentration gradient of salt in the translocation of polyelectrolytes (PE) through nanopores explicitly using coarse-grained Langevin dynamics simulations. The mean translocation time is calculated by varying the applied voltage, the pH, and the salt concentration gradient. Changing the pH can alter the electrostatic interaction between the protein pore and the polyelectrolyte chain.

Dynamics of the protein search for targets on DNA in quorum-sensing cells.

Quorum sensing is a bacterial cell-cell communication process that regulates gene expression. The search and binding of the autoinducer molecule (AHL)-bound LuxR-type proteins to specific sites on DNA in quorum-sensing cells in Gram-negative bacteria is a complex process and has been theoretically investigated based on a discrete-state stochastic approach. It is shown that several factors such as the rate of formation of the AHL-bound LuxR protein within the cells and its dissociation to freely diffusing AHL, the diffusion of the latter in and out of the cells, positive feedback loops, and the cell population density play important roles in the protein target search and can control the gene regulation processes.

Influence of Nonspecific Interactions between Proteins and Cytoplasmic Crowders in Facilitated Diffusion of Proteins: Theoretical Insights.

The binding of proteins to their respective specific sites on the DNA through facilitated diffusion serves as the initial step of various important biological processes. While this search process has been thoroughly investigated studies, the cellular environment is complex and may interfere with the protein's search dynamics. The cytosol is heavily crowded, which can potentially modify the search by nonspecifically interacting with the protein that has been mostly overlooked.

A single-molecule stochastic theory of protein-ligand binding in the presence of multiple unfolding/folding and ligand binding pathways.

Protein folding is a biophysical process by which a protein chain is translated to its native (folded) structure through several intermediate states such that the folded conformation becomes biologically functional. This folded protein can again exist in multiple conformations in its native state and its intrinsic conformational fluctuations are responsible for the protein-ligand recognition and binding to form a specific complex. In this study, we introduce an exactly solvable kinetic model based on a discrete stochastic approach to study the protein-ligand binding by taking into account an arbitrary number of the transient intermediates between the unfolded and the native folded state of the protein.

Understanding the Reaction Dynamics on Heterogeneous Catalysts Using a Simple Stochastic Approach.

Recent experimental advances on investigating nanoparticle catalysts with multiple active sites provided a large amount of quantitative information on catalytic processes. These observations stimulated significant theoretical efforts, but the underlying molecular mechanisms are still not well-understood. We introduce a simple theoretical method to analyze the reaction dynamics on catalysts with multiple active sites based on a discrete-state stochastic description and obtain a comprehensive description of the dynamics of chemical reactions on such catalysts.

Simulation Study of the Conformational Properties of Diblock Polyelectrolytes in Salt Solutions.

Coarse-grained molecular dynamics simulations are performed to understand the behavior of diblock polyelectrolytes in solutions of divalent salt by studying the conformations of chains over a wide range of salt concentrations. The polymer molecules are modeled as bead spring chains with different charged fractions and the counterions and salt ions are incorporated explicitly. Upon addition of a divalent salt, the salt cations replace the monovalent counterions, and the condensation of divalent salt cations onto the polyelectrolyte increases, and the chains favor to collapse.

Effect of Memory and Inertial Contribution on Transition-Time Distributions: Theory and Simulations.

Transition paths refer to the time taken by molecules to cross a barrier separating two molecular conformations. In this work, we study how memory, as well as inertial contribution in the dynamics along a reaction coordinate, can affect the distribution of the transition-path time. We use a simple model of dynamics governed by a generalized Langevin equation with a power-law memory along with the inertial term, which was neglected in previous studies, where memory effects were explored only in the overdamped limit.

Pulling a folded polymer through a nanopore.

We investigate the translocation dynamics of a folded linear polymer which is pulled through a nanopore by an external force. To this end, we generalize the iso-flux tension propagation theory for end-pulled polymer translocation to include the case of two segments of the folded polymer traversing simultaneously trough the pore. Our theory is extensively benchmarked with corresponding molecular dynamics (MD) simulations.

Coarse-grained molecular dynamics simulations study of the conformational properties of single polyelectrolyte diblock copolymers.

We use coarse-grained molecular dynamics simulations to study a single di block polyelectrolyte chain in solution. We analyze the conformational properties of the chain and localization of counterions as a function of the charge fraction, backbone stiffness, Bjerrum length, and counterion valence. The interplay between the excluded-volume effects and the electrostatic interactions among charged residues leads to variation in block-polyelectrolyte architecture.

Effect of DNA Conformation on the Protein Search for Targets on DNA: A Theoretical Perspective.

Protein-DNA interactions are important for all biological processes and involve the process of proteins searching for and recognizing specific binding sites on the DNA. Many aspects of the mechanism of the protein search for targets on DNA are not well understood. One important problem is the effect of DNA conformation on the protein search dynamics.

Theoretical Investigations of the Dynamics of Chemical Reactions on Nanocatalysts with Multiple Active Sites.

Recent synthetic advances led to the development of new catalytic particles with well-defined atomic structures and multiple active sites, which are called nanocatalysts. Experimental studies of processes at nanocatalysts uncovered a variety of surprising effects, but the molecular mechanisms of these phenomena remain not well understood. We propose a theoretical method to investigate the dynamics of chemical reactions on catalytic particles with multiple active sites.

Correction to Effect of Substrate Number Fluctuations in Stochastic Enzyme Kinetics.

[This corrects the article DOI: 10.1021/acsomega.8b00611.

Stochastic simulations data for figure 1 and the phase diagram construction for defining monotonic and non-monotonic regimes of the velocity as a function of .

We have compared our theoretical expressions of the normalized reaction velocities with that of simulation data points generated when the substrate fluctuations are present and absent, for the reaction schemes represented in Figure 1 Singh and Chaudhury, 2019 in the general monotonic as well as the conditional non-monotonic limit. We have also constructed the phase diagrams for the schemes given in Figure 1 Singh and Chaudhury, 2019 separating different regimes of the monotonic and the non-monotonic behaviors observed in the reaction rate.

Translocation Dynamics of an Asymmetrically Charged Polymer through a Pore under the Influence of Different pH Conditions.

We study the translocation of a polymer with oppositely charged segments at both ends of the chain passing through a pore under the effect of an external electric field in the presence of a pH gradient using Langevin dynamics simulations. As observed in experiments, the electrostatic interactions between the pore and the polymer are tuned by altering the pH gradient. Our simulation studies show that with the change in charge distribution on the polymer and the pore that can mimic different pH conditions, the external driving force and the polymer-pore electrostatic interactions play a significant role in the translocation process.