<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Tammara, Vaishnavi</style></author><author><style face="normal" font="default" size="100%">Das, Atanu</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Governing dynamics and preferential binding of the AXH domain influence the aggregation pathway of Ataxin-1</style></title><secondary-title><style face="normal" font="default" size="100%">Proteins-Structure Function and Bioinformatics</style></secondary-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Ataxin-1</style></keyword><keyword><style  face="normal" font="default" size="100%">molecular dynamics simulation</style></keyword><keyword><style  face="normal" font="default" size="100%">neurodegenerative diseases</style></keyword><keyword><style  face="normal" font="default" size="100%">Protein aggregation</style></keyword><keyword><style  face="normal" font="default" size="100%">protein misfolding disorders</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2023</style></year><pub-dates><date><style  face="normal" font="default" size="100%">MAR</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">91</style></volume><pages><style face="normal" font="default" size="100%">380-394</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;
	The present state of understanding the mechanism of Spinocerebellar Ataxia-1, a fatal neurodegenerative disease linked to the protein Ataxin-1 (ATXN1), is baffled by a set of self-contradictory, and hence, inconclusive observations. This fallacy poses a bottleneck to the effective designing of curable drugs as the field is currently missing the specific druggable site. To understand the fundamentals of pathogenesis, we tried to decipher the intricacies of the extremely complicated landscape by targeting the relevant species that supposedly dictate the structure-function paradigm. The atomic-level description and characterization of the dynamism of the systems reveal the existence of structural polymorphism in all the leading stakeholders of the overall system. The very existence of conformational heterogeneity in every species creates numerous possible combinations of favorable interactions because of the variability in segmental cross-talks and hence claims its role in the choice of routes between functional activity and dysfunctional disease-causing aggregation. Despite this emergent configurational diversity, there is a common mode of operative intermolecular forces that dictates the extent of stability of all the multimeric complexes due to the localized population of a specific type of residue. The present research proposes a dynamic switch mechanism between aggregability and functional activity, based on the logical interpretation of the estimated variables, which is practically dictated by the effective concentration of the interacting species involved in the cell.&lt;/p&gt;
</style></abstract><issue><style face="normal" font="default" size="100%">3</style></issue><work-type><style face="normal" font="default" size="100%">Article</style></work-type><custom3><style face="normal" font="default" size="100%">&lt;p&gt;
	Foreign&lt;/p&gt;
</style></custom3><custom4><style face="normal" font="default" size="100%">&lt;p&gt;
	4.088&lt;/p&gt;
</style></custom4></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Tammara, Vaishnavi</style></author><author><style face="normal" font="default" size="100%">Das, Atanu</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Molecular mechanism of PSMa3 aggregation: a new view</style></title><secondary-title><style face="normal" font="default" size="100%">Journal of Physical Chemistry B</style></secondary-title></titles><dates><year><style  face="normal" font="default" size="100%">2023</style></year><pub-dates><date><style  face="normal" font="default" size="100%">SEP</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">127</style></volume><pages><style face="normal" font="default" size="100%">8317-8330</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;
	The emergence of a novel cross-alpha fibrillar structure, unlike the commonly observed sequence-independent cross-beta one, of a 22-residue bacterial virulent amphipathic alpha-helical peptide of the phenol soluble modulin (PSM) family, PSM alpha 3, with many deleterious effects on human life, has infused uncertainty to the paradigm of the intrinsically polymorphic, multivariate, multiphasic, and cross-sequence-cross-disease entangled protein aggregation landscape and hence on the identity of the therapeutic target. We, here, deconvolute the factors contributing to the genesis and hence the transition of lower to higher order aggregates of PSM alpha 3 in its natural state and three noncanonical designed variants using conventional and enhanced sampling approach-based atomistic simulations. PSM alpha 3 shows structural polymorphism with nominal alpha-helicity, substantial beta-propensity, and dominant random-coil features, irrespective of the extent of aggregation. Moreover, the individual features of the overall amphipathicity operate alternatively depending on the extent and organization of aggregation; the dominance gradually moves from charged to hydrophobic residues with the progressive generation of higher order aggregates (dimer to oligomer to fibril) and with increasing orderedness of the self-assembled construct (oligomer vs dimer/fibril). Similarly, the contribution of interchain salt bridges decreases with increasing order of aggregation (dimer to oligomer to fibril). However, the intrachain salt bridges consistently display their role in all phases of aggregation. Such phase-independent features also include equivalent roles of electrostatic and van der Waals forces on intrachain interactions, sole contribution of van der Waals forces on interchain cross-talk, and negligible peptide-water relationship. Finally, we propose a conjugate peptide-based aggregation suppressor having a single-point proline mutation.&lt;/p&gt;
</style></abstract><issue><style face="normal" font="default" size="100%">39</style></issue><work-type><style face="normal" font="default" size="100%">Article</style></work-type><custom3><style face="normal" font="default" size="100%">&lt;p&gt;
	Foreign&lt;/p&gt;
</style></custom3><custom4><style face="normal" font="default" size="100%">&lt;p&gt;
	3.3&lt;/p&gt;
</style></custom4></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Tammara, Vaishnavi</style></author><author><style face="normal" font="default" size="100%">Doke, Abhilasha A.</style></author><author><style face="normal" font="default" size="100%">Jha, Santosh Kumar</style></author><author><style face="normal" font="default" size="100%">Das, Atanu</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Deciphering the monomeric and dimeric conformational landscapes of the full-length TDP-43 and the impact of the C-terminal domain</style></title><secondary-title><style face="normal" font="default" size="100%">ACS Chemical Neuroscience</style></secondary-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">chain collapsibility</style></keyword><keyword><style  face="normal" font="default" size="100%">domain-wisefluctuation</style></keyword><keyword><style  face="normal" font="default" size="100%">electrostatic dominance</style></keyword><keyword><style  face="normal" font="default" size="100%">hydrogen bond switchability</style></keyword><keyword><style  face="normal" font="default" size="100%">long-range crosstalk</style></keyword><keyword><style  face="normal" font="default" size="100%">persistent beta-character</style></keyword><keyword><style  face="normal" font="default" size="100%">protagonistic C-terminal domain</style></keyword><keyword><style  face="normal" font="default" size="100%">rugged phase space</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2024</style></year><pub-dates><date><style  face="normal" font="default" size="100%">NOV</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">15</style></volume><pages><style face="normal" font="default" size="100%">4305-4321</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;
	The aberrant aggregation of TAR DNA-binding protein 43 kDa (TDP-43) in cells leads to the pathogenesis of multiple fatal neurodegenerative diseases. Decoding the proposed initial transition between its functional dimeric and aggregation-prone monomeric states can potentially design a viable therapeutic strategy, which is presently limited by the lack of structural detail of the full-length TDP-43. To achieve a complete understanding of such a delicate phase space, we employed a multiscale simulation approach that unearths numerous crucial features, broadly summarized in two categories: (1) state-independent features that involve inherent chain collapsibility, rugged polymorphic landscape dictated by the terminal domains, high beta-sheet propensity, structural integrity preserved by backbone-based intrachain hydrogen bonds and electrostatic forces, the prominence of the C-terminal domain in the intrachain cross-domain interfaces, and equal participation of hydrophobic and hydrophilic (charged and polar) residues in cross-domain interfaces; and (2) dimerization-modulated characteristics that encompass slower collapsing dynamics, restricted polymorphic landscape, the dominance of side chains in interchain hydrogen bonds, the appearance of the N-terminal domain in the dimer interface, and the prominence of hydrophilic (specifically polar) residues in interchain homo- and cross-domain interfaces. In our work, the ill-known C-terminal domain appears as the most crucial structure-dictating domain, which preferably populates a compact conformation with a high beta-sheet propensity in its isolated state stabilized by intrabackbone hydrogen bonds, and these signatures are comparatively faded in its integrated form. Validation of our simulated observables by a complementary spectroscopic approach on multiple counts ensures the robustness of the computationally predicted features of the TDP-43 aggregation landscape.&lt;/p&gt;
</style></abstract><work-type><style face="normal" font="default" size="100%">Article</style></work-type><custom3><style face="normal" font="default" size="100%">&lt;p&gt;
	Foreign&lt;/p&gt;
</style></custom3><custom4><style face="normal" font="default" size="100%">&lt;p&gt;
	5&lt;/p&gt;
</style></custom4></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Tammara, Vaishnavi</style></author><author><style face="normal" font="default" size="100%">Angrover, Ruchika</style></author><author><style face="normal" font="default" size="100%">Sirur, Disha</style></author><author><style face="normal" font="default" size="100%">Das, Atanu</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Flagellar motor protein-targeted search for the druggable site of Helicobacter pylori</style></title><secondary-title><style face="normal" font="default" size="100%">Physical Chemistry Chemical Physics </style></secondary-title></titles><dates><year><style  face="normal" font="default" size="100%">2024</style></year><pub-dates><date><style  face="normal" font="default" size="100%">JAN </style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">26</style></volume><pages><style face="normal" font="default" size="100%">2111-2126</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;
	The deleterious impact of Helicobacter pylori (H. pylori) on human health is contingent upon its ability to create and sustain colony structure, which in turn is dictated by the effective performance of flagella - a multi-protein rotary nanodevice. Hence, to design an effective therapeutic strategy against H. pylori, we here conducted a systematic search for an effective druggable site by focusing on the structure-dynamics-energetics-stability landscape of the junction points of three 1 : 1 protein complexes (FliF(C)-FliG(N), FliG(M)-FliM(M), and FliY(C)-FliN(C)) that contribute mainly to the rotary motion of the flagella via the transformation of information along the junctions over a wide range of pH values operative in the stomach (from neutral to acidic). We applied a gamut of physiologically relevant perturbations in the form of thermal scanning and mechanical force to sample the entire quasi - and non-equilibrium conformational spaces available for the protein complexes under neutral and acidic pH conditions. Our perturbation-induced magnification of conformational distortion approach identified pH-independent protein sequence-specific evolution of precise thermally labile segments, which dictate the specific thermal unfolding mechanism of each complex and this complex-specific pH-independent structural disruption notion remains consistent under mechanical stress as well. Complementing the above observations with the relative rank-ordering of estimated equilibrium binding free energies between two protein sequences of a specific complex quantifies the extent of structure-stability modulation due to pH alteration, rationalizes the exceptional stability of H. pylori under acidic pH conditions, and identifies the pH-independent complex-sequence-segment-residue diagram for targeted drug design.&lt;/p&gt;
</style></abstract><issue><style face="normal" font="default" size="100%">3</style></issue><work-type><style face="normal" font="default" size="100%">Article</style></work-type><custom3><style face="normal" font="default" size="100%">&lt;p&gt;
	Foreign&lt;/p&gt;
</style></custom3><custom4><style face="normal" font="default" size="100%">&lt;p&gt;
	3.3&lt;/p&gt;
</style></custom4></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Tammara, Vaishnavi</style></author><author><style face="normal" font="default" size="100%">Das, Atanu</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Self-consistent molecular mechanism of β2-microglobulin aggregation</style></title><secondary-title><style face="normal" font="default" size="100%">Journal of Physical Chemistry B</style></secondary-title></titles><dates><year><style  face="normal" font="default" size="100%">2024</style></year><pub-dates><date><style  face="normal" font="default" size="100%">DEC</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">128</style></volume><pages><style face="normal" font="default" size="100%">12425-12442</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;
	Despite the consensus on the origin of dialysis-related amyloidosis (DRA) being beta(2)-microglobulin (beta(2)m) aggregation, the debate on the underlying mechanism persists because of the continuous emergence of beta(2)m variant- and pH-dependent contradictory results. By characterizing the native monomeric (initiation) and aggregated fibrillar (termination) states of beta(2)m via a combination of two enhanced sampling approaches, we here propose a mechanism that explains the heterogeneous behavior of wild-type (WT) and pathogenic (V27M and D76N) beta(2)m variants in physiological and disease-pertinent acidic pH environments. It appears that the higher retainment of monomeric native folds at neutral pH (native-like) distinguishes pathogenic beta(2)m mutants from the WT (moderate loss). However, at acidic pH, all three variants behave similarly in producing a substantial amount of partially unfolded states (conformational switch, propensity), though with different extents (WT &amp;lt; V27M &amp;lt; D76N). Whereas at the fibrillar end, all beta(2)m variants display a pH-dependent protofilament separation pathway and a higher protofilament binding affinity (stability) at acidic pH, where the relative order of binding affinity (WT &amp;lt; V27M &amp;lt; D76N) remains consistent with pH modulation. Combining these observations, we conclude that beta(2)m variants possibly shift from native-like aggregation to conformational switch-initiated fibrillation as the pH is altered from neutral to acidic. The combined propensity-stability approach based on the initiation and termination points of beta(2)m aggregation not only assists us in deciphering the mechanism but also emphasizes the protagonistic roles of both terminal points in the overall aggregation process.&lt;/p&gt;
</style></abstract><issue><style face="normal" font="default" size="100%">50</style></issue><work-type><style face="normal" font="default" size="100%">Article</style></work-type><custom3><style face="normal" font="default" size="100%">&lt;p&gt;
	Foreign&lt;/p&gt;
</style></custom3><custom4><style face="normal" font="default" size="100%">&lt;p&gt;
	3.3&lt;/p&gt;
</style></custom4></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Sheikh, Amreen B.</style></author><author><style face="normal" font="default" size="100%">Jathar, Swaraj M.</style></author><author><style face="normal" font="default" size="100%">Tammara, Vaishnavi</style></author><author><style face="normal" font="default" size="100%">Das, Atanu</style></author><author><style face="normal" font="default" size="100%">Kulkarni, Mahesh J.</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Characterization of S-homocysteinylation of Human Insulin and Its Implications in Diabetes</style></title><secondary-title><style face="normal" font="default" size="100%">Protein Journal</style></secondary-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Disulfide bonds</style></keyword><keyword><style  face="normal" font="default" size="100%">Homocysteinylation</style></keyword><keyword><style  face="normal" font="default" size="100%">insulin</style></keyword><keyword><style  face="normal" font="default" size="100%">Mass spectrometry</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2025</style></year><pub-dates><date><style  face="normal" font="default" size="100%">OCT</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">44</style></volume><pages><style face="normal" font="default" size="100%">598-610</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;
	Homocysteine thiolactone is a reactive thiol known for its interaction with various proteins. Nevertheless, there exists a paucity of information concerning the interaction between homocysteine thiolactone and human insulin, particularly regarding the mechanism by which homocysteine facilitates the reduction of disulfide bonds within insulin. In the present study, we have elucidated the binding sites of homocysteine to the cysteine residues (A6-B7 and A20-B19) that are implicated in the formation of intermolecular disulfide bonds in insulin through an in vitro reaction analyzed via LC-ESI MS/MS. This results in a reduction of disulfide bonds linking the A and B chains, which was corroborated by MALDI-TOF-MS and ESI-MS analysis. The secondary structure of insulin is affected by this modification, as evidenced by circular dichroism spectroscopy. In-silico studies also show that homocysteine affects the insulin structure. A glucose uptake assay conducted in Chinese hamster ovary (CHO) cells that stably express the insulin receptor revealed that HC-modified insulin is less effective in inducing glucose uptake compared to native insulin, suggesting that HC-induced structural modifications in insulin influence functional activity. This study provides insight into the HC-induced structural and functional changes in insulin and discusses the consequent implications for diabetes.&lt;/p&gt;
</style></abstract><issue><style face="normal" font="default" size="100%">5</style></issue><work-type><style face="normal" font="default" size="100%">Article</style></work-type><custom3><style face="normal" font="default" size="100%">&lt;p&gt;
	Foreign&lt;/p&gt;
</style></custom3><custom4><style face="normal" font="default" size="100%">&lt;p&gt;
	2.3&lt;/p&gt;
</style></custom4></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Tammara, Vaishnavi</style></author><author><style face="normal" font="default" size="100%">Das, Atanu</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Decoding the relationship between alzheimer's disease and type-2 diabetes via the protein aggregation prism</style></title><secondary-title><style face="normal" font="default" size="100%">ACS Chemical Neuroscience</style></secondary-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">amylin</style></keyword><keyword><style  face="normal" font="default" size="100%">Amyloid-beta</style></keyword><keyword><style  face="normal" font="default" size="100%">liquid-liquidphase separation</style></keyword><keyword><style  face="normal" font="default" size="100%">Oligomer</style></keyword><keyword><style  face="normal" font="default" size="100%">self vs cross-aggregation</style></keyword><keyword><style  face="normal" font="default" size="100%">unseeded vs seeded aggregation</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2025</style></year><pub-dates><date><style  face="normal" font="default" size="100%">AUG </style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">16</style></volume><pages><style face="normal" font="default" size="100%">3003-3019</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;
	Alzheimer's disease (AD) and type-2 diabetes (T2D) are two fatal human diseases and have been linked to the aberrant aggregation of two distinct peptides, amyloid-beta (A beta) and human islet amyloid polypeptide (hIAPP), respectively. These two peptide aggregates, even with distal deposition sites (brain and pancreas), act as mutual beneficiaries. We here unveiled the crosstalk in a self-consistent fashion using atomistic simulations by comparing the kinetics and thermodynamics of self- and cross-aggregations of A beta(42) and hIAPP and their modulations by preformed fibrillar templates. Templates (specifically hIAPP) generally accelerate aggregation, alter the relative order of aggregation rates (cross-aggregation &amp;gt; A beta self-aggregation &amp;gt; hIAPP self-aggregation for nontemplated and hIAPP self-aggregation &amp;gt; cross-aggregation &amp;gt; A beta self-aggregation for templated), and flip the mutual impact (hIAPP aggravates A beta aggregation in nontemplated and the reverse in templated). Higher instances of breaking larger aggregates and longer residence times of smaller aggregates decelerate aggregation, whereas interpeptide electrostatics (universal) and hydrogen bonds (templated) assist it. However, the equilibrium aggregability pattern contradicts kinetic rank-ordering, as A beta displays a higher aggregability than hIAPP, templates increase aggregability for both peptides, and A beta's self-aggregability supersedes cross-aggregability, which further surpasses hIAPP's self-aggregability. The equilibrium ensembles encompass polymorphic, nonfibrillar oligomers having substantially reduced alpha-helicity and slight beta-propensity, with both parallel and antiparallel interpeptide orientations, primarily stabilized by electrostatics. A higher equilibrium aggregability means a greater helix-breaking capacity, a bias toward parallel orientation, and a lesser structural polymorphism. Water expulsion from peptide surroundings and distortion of water tetrahedrality prove that aggregation follows the liquid-liquid phase separation (LLPS) model.&lt;/p&gt;
</style></abstract><issue><style face="normal" font="default" size="100%">15</style></issue><work-type><style face="normal" font="default" size="100%">Article</style></work-type><custom3><style face="normal" font="default" size="100%">&lt;p&gt;
	Foreign&lt;/p&gt;
</style></custom3><custom4><style face="normal" font="default" size="100%">&lt;p&gt;4.0&lt;/p&gt;
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