arXiv subjects

Jagannath Mondal

Publications and source records attributed to Jagannath Mondal.

7 recordsLinked to original sources

arXiv2026

Reaction-transport coupling drives spatiotemporal organization in fuel-driven supramolecular polymerization

Chemically fueled supramolecular systems provide a versatile platform for generating nonequilibrium structures and dynamical instabilities, including chemical oscillations and traveling waves reminiscent of biological organization. However, a minimal mechanistic framework capable of capturing the emergence of such spatiotemporal order is still lacking. Here, we develop a minimal reaction-transport framework for fuel-driven supramolecular polymerization that couples activation-deactivation chemistry with cooperative assembly, fragmentation, and polymer length-dependent diffusion. The model captures autonomous oscillations arising through a Hopf bifurcation and demonstrates how temporal instabilities evolve into spatial self-organization upon inclusion of transport. We show that the nonlinear interplay between reaction kinetics and state-dependent mobility gives rise to traveling polymerization fronts, oscillatory wave dynamics, and complex spatiotemporal patterns. The propagating fronts exhibit near-ballistic dynamics, revealing a fundamentally nonequilibrium transport mechanism emerging from reactive feedback and dynamically evolving diffusivity. These findings establish a minimal physical framework connecting dissipative self-assembly, nonlinear transport, and active matter, while providing design principles for programmable supramolecular materials capable of autonomous spatiotemporal organization.

cond-mat.soft↗

arXiv2021

A Deep Autoencoder Framework for Discovery of Metastable Ensembles in Biomacromolecules

Mini-proteins and peptides manifest dynamic conformational fluctuation and involve mutual interconversion among metastable states. A robust mapping of the conformational landscape underlying mini-proteins and peptides often requires low-dimensional projection of the conformational ensemble along optimized collective variables. However, the traditional choice for the collective variable (CV) is often limited by user-intuition and prior knowledge about the system, which lacks a rigorous assessment of their optimality over other candidate CVs. To address this issue, we propose a generic approach in which we first choose the possible combinations of inter-residue Calpha-distances within a given macromolecule as a set of input CVs. Subsequently we derive a non-linear combination of latent-space embedded collective variables via auto-encoding the unbiased MD simulation trajectories within the framework of feed-forward neural network. We demonstrate the ability of the derived latent space variables in elucidating the conformational landscape in three hierarchically complex systems. When the conformational dynamics is resolved along the latent space CVs, it identifies key metastable states of a bead-in-a-spring polymer. The combination of the adopted dimensionally reduction technique with a Markov state model, built on the derived latent space, efficiently projects the free energy landscape of GB1 beta-hairpin, revealing multiple spatially well-resolved and kinetically well-separated metastable conformations. A quantitative comparison based on variational approach to Markov Process of the auto encoder-derived latent-space CVs with the ones obtained PCA or TICA confirms the optimality of the former. Finally, as a practical application, we demonstrate that the auto-encoder derived CVs successfully predict the reinforced folding of Trp-cage mini-protein in an aqueous osmolyte solution.

physics.chem-ph↗

arXiv2019

On the Role of Solvent in Hydrophobic Cavity-ligand Recognition Kinetics

Solvent often manifests itself as the key determinant of the kinetic aspect of molecular recognition process. While the solvent is often depicted as a source of barrier in the ligand recognition process by polar cavity, the nature of solvent's role in the recognition process involving hydrophobic cavity and hydrophobic ligand remains to be addressed. In this work, we quantitatively assess the role of solvent in dictating the kinetic process of recognition in a popular system involving hydrophobic cavity and ligand. In this prototypical system the hydrophobic cavity undergoes \textit{dewetting transition} as the ligand approaches the cavity, which influences the cavity-ligand recognition kinetics. Here, we build Markov state model (MSM) using adaptively sampled unrestrained molecular dynamics simulation trajectories to map the kinetic recognition process. The MSM-reconstructed free energy surface recovers a broad water distribution at an intermediate cavity-ligand separation, consistent with previous report of dewetting transition in this system. Time-structured independent component analysis of the simulated trajectories quantitatively shows that cavity-solvent density contributes considerably in an optimised reaction coordinate involving cavity-ligand separation and water occupancy. Our approach quantifies two solvent-mediated macro states at an intermediate separation of the cavity-ligand recognition pathways, apart from the fully ligand-bound and fully ligand-unbound macro states. Interestingly, we find that these water-mediated intermediates, while transient in populations, can undergo slow mutual interconversion and create possibilities of multiple pathways of cavity recognition by the ligand. Overall, the work provides a quantitative assessment of the role that solvent plays in facilitating the recognition process involving hydrophobic cavity.

physics.chem-ph↗

arXiv2017

Role of $α$ and $β$ relaxations in Collapsing Dynamics of a Polymer Chain in Supercooled Glass-forming Liquid

Understanding the effect of glassy dynamics on the stability of bio-macromolecules and investigating the underlying relaxation processes governing degradation processes of these macromolecules are of immense importance in the context of bio-preservation. In this work we have studied the stability of a model polymer chain in a supercooled glass-forming liquid at different amount of supercooling in order to understand how dynamics of supercooled liquids influence the collapse behavior of the polymer. Our systematic computer simulation studies find that apart from long time relaxation processes ($α$ relaxation), short time dynamics of the supercooled liquid, known as $β$ relaxation plays an important role in controlling the stability of the model polymer. This is in agreement with some recent experimental findings. These observations are in stark contrast with the common belief that only long time relaxation processes are the sole player. We find convincing evidence that suggest that one might need to review the the vitrification hypothesis which postulates that $α$ relaxations control the dynamics of biomolecules and thus $α$-relaxation time should be considered for choosing appropriate bio-preservatives. We hope that our results will lead to understand the primary factors in protein stabilization in the context of bio-preservation.

cond-mat.soft↗

arXiv2015

The role of water and steric constraints in the kinetics of cavity-ligand unbinding

A key factor influencing a drug's efficacy is its residence time in the binding pocket of the host protein. Using atomistic computer simulation to predict this residence time and the associated dissociation process is a desirable but extremely difficult task due to the long timescales involved. This gets further complicated by the presence of biophysical factors such as steric and solvation effects. In this work, we perform molecular dynamics (MD) simulations of the unbinding of a popular prototypical hydrophobic cavity-ligand system using a metadynamics based approach that allows direct assessment of kinetic pathways and parameters. When constrained to move in an axial manner, we find the unbinding time to be on the order of 4000 sec. In accordance with previous studies, we find that the ligand must pass through a region of sharp dewetting transition manifested by sudden and high fluctuations in solvent density in the cavity. When we remove the steric constraints on ligand, the unbinding happens predominantly by an alternate pathway, where the unbinding becomes 20 times faster, and the sharp dewetting transition instead becomes continuous. We validate the unbinding timescales from metadynamics through a Poisson analysis, and by comparison through detailed balance to binding timescale estimates from unbiased MD. This work demonstrates that enhanced sampling can be used to perform explicit solvent molecular dynamics studies at timescales previously unattainable, obtaining direct and reliable pictures of the underlying physio-chemical factors including free energies and rate constants.

cond-mat.soft↗

arXiv2013

How hydrophobic drying forces impact the kinetics of molecular recognition

A model of protein-ligand binding kinetics in which slow solvent dynamics results from hydrophobic drying transitions is investigated. Molecular dynamics simulations show that solvent in the receptor pocket can fluctuate between wet and dry states with lifetimes in each state that are long enough for the extraction of a separable potential of mean force and wet-to-dry transitions. We introduce a Diffusive Surface Hopping Model that is represented by a two-dimensional Markovian master equation. One dimension is the standard reaction coordinate, the ligand-pocket separation, and the other is the solvent state in the region between ligand and binding pocket which specifies whether it is wet or dry. In our model, the ligand diffuses on a dynamic free energy surface which undergoes kinetic transitions between the wet and dry states. The model yields good agreement with results from explicit solvent molecular dynamics simulation and an improved description of the kinetics of hydrophobic assembly. Furthermore, it is consistent with a "non-Markovian Brownian theory" for the ligand-pocket separation coordinate alone.

cond-mat.soft↗

arXiv2013

When does TMAO fold a polymer chain and urea unfold it?

Longstanding mechanistic questions about the role of protecting osmolyte trimethylamine N- oxide (TMAO) which favors protein folding and the denaturing osmolyte urea are addressed by studying their effects on the folding of uncharged polymer chains. Using atomistic molecular dynamics simulations, we show that 1-M TMAO and 7-M urea solutions act dramatically differently on these model polymer chains. Their behaviors are sensitive to the strength of the attractive dispersion interactions of the chain with its environment: when these dispersion interactions are high enough, TMAO suppresses the formation of extended conformations of the hydrophobic polymer as compared to water, while urea promotes formation of extended conformations. Similar trends are observed experimentally on real protein systems. Quite surprisingly, we find that both protecting and denaturing osmolytes strongly interact with the polymer, seemingly in contrast with existing explanations of the osmolyte effect on proteins. We show that what really matters for a protective osmolyte is its effective depletion as the polymer conformation changes, which leads to a negative change in the preferential binding coefficient. For TMAO, there is a much more favorable free energy of insertion of a single osmolyte near collapsed conformations of the polymer than near extended conformations. By contrast, urea is preferentially stabilized next to the extended conformation and thus has a denaturing effect.

physics.bio-ph↗