Neelanjana Sengupta

Externally imposed perturbations can subtly reshape protein structure and mechanics prior to the emergence of global unfolding signatures. Delineating locally sensitive zones, however, can pose immense challenges. Subjecting a small folded protein to isotropic pressure spanning 0.001–10 kbar, we develop a simplified and interpretable computational framework to characterize local responses embedded within its conformational ensemble. Pairwise mechanical stiffness descriptors are treated as high-dimensional mechanical fingerprints and projected using linear discriminant analysis (LDA) to identify the pressure ranges that maximally separate conformational populations. To attribute the discriminative mechanical changes to specific residues, we combine the LDA model with SHapley Additive exPlanations, yielding a ranked set of locally responsive sites. While the overall rigidity landscape of the protein shows only modest pressure dependence, the top-ranked residues exhibit pronounced, pressure-specific alterations in solvent association. Radial distribution functions and tetrahedral order metrics reveal significant reorganization of hydration structure around the leading hotspot across the LDA-inferred transition region, whereas low-ranked sites display weak or nonspecific hydration changes. Together, these results connect global thermodynamic perturbation to localized mechanical and hydration responses and suggest a practical route for prioritizing mutation sites and mechanistic hypotheses in perturbed biomolecular systems.

β-Glucosidases are essential for lignocellulosic biomass conversion, yet their industrial utility is limited by inhibition from glucose, the reaction product. Although glucose inhibition has been extensively documented, its molecular basis remains poorly understood. Here, we demonstrate that glucose inhibition in the GH1 β-glucosidase BglB from Paenibacillus polymyxa is mediated by multiple surface-exposed secondary binding sites (SBSs) that function as regulatory elements rather than passive glucose-binding patches. Kinetic analyses revealed a mixed mode of inhibition, with modest activation at low glucose concentrations followed by progressive inhibition at higher concentrations. Glucose association occurred through multiple SBSs in a concentration-dependent manner and induced localized rigidification, particularly at gatekeeper regions surrounding the active-site entrance. These surface interactions propagated through long-range coupling pathways, resulting in structural, energetic, and residue interaction network reorganization that reshaped the catalytic pocket. Functional interrogation of representative SBSs revealed distinct roles for individual sites. Mutation of a gatekeeper-associated SBS reduced local glucose association, increased glucose tolerance by more than 30%, and improved substrate affinity by approximately 38%, whereas disruption of a distal SBS compromised structural integrity and soluble protein production. Together, these findings establish a direct link between surface glucose recognition and active-site regulation, providing, to our knowledge, the first integrated evidence for the existence and functional significance of secondary glucose-binding sites in β-glucosidases. More broadly, this work identifies surface SBSs as promising targets for engineering glucose-tolerant and catalytically robust enzymes for biomass conversion and related biotechnological applications.

Peptide‐based functional biomaterials have attracted widespread interest due to their inherent biocompatibility, biodegradability, and structural tunability. Among functional biomaterials, piezoelectric materials are particularly valuable for developing self‐powered biodevices in biomedical applications. However, peptide‐based piezoresponsive systems remain largely underexplored. In this study, we present a chromophore‐conjugated peptide (PEP‐A) that self‐assembles into nanomaterials exhibiting either piezo‐active or inactive states, with the functional behaviour closely linked to their chiroptical properties under different solvent conditions. Through a comprehensive investigation involving spectroscopy, microscopy, and atomistic simulations, we uncover how cosolvent‐induced modulation of the self‐assembly process co‐governs chiroptical and piezoelectric properties. Interestingly, PEP‐A forms elongated nanofibers in pure water that are both chiroptically and piezoelectrically inactive. However, the introduction of a minimal amount of cosolvent (1% DMSO or 1% DMF) triggers the emergence of supramolecular chirality alongside a significant piezoresponse, revealing a direct correlation between macroscopic chirality and piezoelectric functionality. Our findings highlight how subtle changes in the assembly environment can drive profound shifts in material properties, offering a powerful strategy to design responsive piezoelectric biomaterials. This study provides a novel approach to designing next‐generation, responsive, peptide‐based piezoelectric biomaterials for biomedical and bioelectronic applications.

Peptide‐based functional biomaterials have attracted widespread interest due to their inherent biocompatibility, biodegradability, and structural tunability. Among functional biomaterials, piezoelectric materials are particularly valuable for developing self‐powered biodevices in biomedical applications. However, peptide‐based piezoresponsive systems remain largely underexplored. In this study, we present a chromophore‐conjugated peptide (PEP‐A) that self‐assembles into nanomaterials exhibiting either piezo‐active or inactive states, with the functional behaviour closely linked to their chiroptical properties under different solvent conditions. Through a comprehensive investigation involving spectroscopy, microscopy, and atomistic simulations, we uncover how cosolvent‐induced modulation of the self‐assembly process co‐governs chiroptical and piezoelectric properties. Interestingly, PEP‐A forms elongated nanofibers in pure water that are both chiroptically and piezoelectrically inactive. However, the introduction of a minimal amount of cosolvent (1% DMSO or 1% DMF) triggers the emergence of supramolecular chirality alongside a significant piezoresponse, revealing a direct correlation between macroscopic chirality and piezoelectric functionality. Our findings highlight how subtle changes in the assembly environment can drive profound shifts in material properties, offering a powerful strategy to design responsive piezoelectric biomaterials. This study provides a novel approach to designing next‐generation, responsive, peptide‐based piezoelectric biomaterials for biomedical and bioelectronic applications.

Methanol–water composition modulates solvation structure and dynamics around calix[4]tyrosols, with enhanced structuring in water-rich media and faster dynamics in methanol-rich mixtures, while conformational stability remains unchanged.

Professors Ashwani K. Tiwari, Balakrishnan Naduvalath, Rotti Srinivasamurthy Swathi and Neelanjana Sengupta introduce this Phys. Chem. Chem. Phys. themed collection Structure and dynamics of chemical systems: Honouring N. Sathyamurthy's 75th birthday.

The design of red-emissive nonconjugated polymers and the interpretation of their photophysical behavior remain a significant challenge in materials chemistry. Clustering-triggered emission (CTE), driven by through-space donor-acceptor (D-A) interactions within polymeric assemblies, is a key principle governing such nonconventional luminescence. Herein, we uncover an unusual red emission from a maleimide-based homopolymer (PM) in aqueous media, arising through CTE. Introduction of in vitro synthesized insulin amyloid fibrils (IAFs) directs this emissive polymer into an OFF-pathway, effectively suppressing its ON-state CTE. Fluorescence spectroscopic studies reveal that PM functions as a ratiometric probe for IAFs, where the β-sheet fibril architecture modulates CTE through supramolecular interactions and disrupted clustering. Complementary molecular dynamics (MD) simulations further demonstrate that the emission arises from a delicate balance of intra- and intermolecular interactions within polymer clusters, which become perturbed upon amyloid binding. Together, these findings provide mechanistic insight into CTE in nonconjugated systems and establish a foundation for developing water-soluble luminescent probes for selective amyloid detection and broader biomedical applications.