01488nas a2200217 4500008004100000022001400041245013800055210006900193260005700262300001200319490000700331520063900338653001800977653002000995653001901015653003401034653002701068100002401095700002501119856012601144 2012 eng d a0175-757100aEffect of the A30P mutation on the structural dynamics of micelle-bound alpha synuclein released in water: a molecular dynamics study0 aEffect of the A30P mutation on the structural dynamics of micell a233 SPRING ST, NEW YORK, NY 10013 USAbSPRINGERcMAY a483-4890 v413 a

Atomistic molecular dynamics simulation has been used to probe the effect of the A30P mutation on the structural dynamics of micelle-bound, helical alpha Synuclein when released in an aqueous environment. On the timescales simulated, the effect of the mutation on the secondary structure is restricted to local changes close to the mutation site in the N-terminal helical domain. The changes are transient, and all residues except Lys23 recover their initial structure. The local behavior due to the mutation gives rise to a global difference in the A30P mutant in the form of a permanent kink in the N-terminal helical domain.

10aA30P mutation10aAlpha synuclein10aKink formation10amolecular dynamics simulation10aStructural persistence1 aChatterjee, Prathit1 aSengupta, Neelanjana uhttp://library.ncl.res.in/content/effect-a30p-mutation-structural-dynamics-micelle-bound-alpha-synuclein-released-water-001490nas a2200205 4500008004100000022001400041245016300055210006900218260005700287300001200344490000700356520065200363653001701015653002601032653003401058653002401092100001901116700002501135856012401160 2013 eng d a0175-757100aMolecular dynamics simulation studies of the structural response of an isolated A beta(1-42) monomer localized in the vicinity of the hydrophilic TiO2 surface0 aMolecular dynamics simulation studies of the structural response a233 SPRING ST, NEW YORK, NY 10013 USAbSPRINGERcJUN a487-4940 v423 a

We have probed the effect of a model hydrophilic surface, rutile TiO2, on the full-length amyloid beta (A beta(1-42)) monomer using molecular dynamics simulations. The rutile surface brings about sharp changes in the peptide's intrinsic behavior in a distance-dependent manner. The intrinsic collapse of the peptide is disrupted, while the beta-sheet propensity is sharply enhanced with increased proximity to the surface. The results may have implications for A beta self-assembly and fibrillogenesis on hydrophilic surfaces and should be taken into consideration in the design of novel nanomaterials for perturbing amyloidogenic behavior.

10aAmyloid beta10abeta-Sheet propensity10amolecular dynamics simulation10aTiO2 rutile surface1 aJose, Jaya, C.1 aSengupta, Neelanjana uhttp://library.ncl.res.in/content/molecular-dynamics-simulation-studies-structural-response-isolated-beta1-42-monomer-002055nas a2200229 4500008004100000022001400041245012700055210006900182260007300251300001200324490000800336520116700344653001501511653002501526653002001551653002101571653003401592653002901626100001901655700002501674856012601699 2013 eng d a0301-462200aSurface induced collapse of A beta(1-42) with the F19A replacement following adsorption on a single walled carbon nanotube0 aSurface induced collapse of A beta142 with the F19A replacement  aPO BOX 211, 1000 AE AMSTERDAM, NETHERLANDSbELSEVIER SCIENCE BVcDEC a108-1150 v1843 a

Spontaneous adsorption of the A beta peptide on the surface of a single-walled carbon nanotube, resulting in the prevention of its intrinsic propensity to form collapsed states, could be a plausible means to hinder the peptide's initial nucleation and self-assembly. We report here the effects of sharply reducing both aromatic and hydrophobic character within the peptide's central hydrophobic core on its free and surface behavior. In such an altered peptide, complete surface adsorption is found to induce, rather than prevent, the adsorbed peptide's collapse. The weakened surface interactions of the central hydrophobic core allow its greater translational mobility on the surface, thereby facilitating interactions that lead to compaction. Both the adsorption and the subsequent collapse are accompanied by a loss of surface hydration in the modified peptide. We further find that such a two-step dewetting leads to hydration levels comparable to that obtained after compaction of the free peptide. These insights may be leveraged for designing molecular surfaces for disrupting intrinsic A beta behavior. (C) 2013 Elsevier B.V. All rights reserved.

10aAdsorption10aAmyloid beta peptide10acarbon nanotube10aLateral mobility10amolecular dynamics simulation10aSurface induced collapse1 aJana, Asis, K.1 aSengupta, Neelanjana uhttp://library.ncl.res.in/content/surface-induced-collapse-beta1-42-f19a-replacement-following-adsorption-single-walled-002356nas a2200265 4500008004100000022001400041245015900055210006900214260009200283300001200375490000700387520131600394653000901710653002501719653003401744653002701778100002201805700002301827700002001850700002101870700002001891700002201911700002801933856012901961 2015 eng d a0968-768800aDifferential dynamics of the serotonin(1A) receptor in membrane bilayers of varying cholesterol content revealed by all atom molecular dynamics simulation0 aDifferential dynamics of the serotonin1A receptor in membrane bi a4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLANDbTAYLOR & FRANCIS LTDcMAY a127-1370 v323 a

The serotonin(1A) receptor belongs to the superfamily of G protein-coupled receptors (GPCRs) and is a potential drug target in neuropsychiatric disorders. The receptor has been shown to require membrane cholesterol for its organization, dynamics and function. Although recent work suggests a close interaction of cholesterol with the receptor, the structural integrity of the serotonin(1A) receptor in the presence of cholesterol has not been explored. In this work, we have carried out all atom molecular dynamics simulations, totaling to 3s, to analyze the effect of cholesterol on the structure and dynamics of the serotonin(1A) receptor. Our results show that the presence of physiologically relevant concentration of membrane cholesterol alters conformational dynamics of the serotonin(1A) receptor and, on an average lowers conformational fluctuations. Our results show that, in general, transmembrane helix VII is most affected by the absence of membrane cholesterol. These results are in overall agreement with experimental data showing enhancement of GPCR stability in the presence of membrane cholesterol. Our results constitute a molecular level understanding of GPCR-cholesterol interaction, and represent an important step in our overall understanding of GPCR function in health and disease.

10aGPCR10aMembrane cholesterol10amolecular dynamics simulation10aserotonin(1A) receptor1 aPatra, Swarna, M.1 aChakraborty, Sudip1 aShahane, Ganesh1 aPrasanna, Xavier1 aSengupta, Durba1 aMaiti, Prabal, K.1 aChattopadhyay, Amitabha uhttp://library.ncl.res.in/content/differential-dynamics-serotonin1a-receptor-membrane-bilayers-varying-cholesterol-content-002808nas a2200265 4500008004100000022001400041245012900055210006900184260010600253300001000359490000700369520184100376653001102217653002002228653002002248653002302268653002202291653003402313653001002347653001402357653001402371100001702385700001902402856012102421 2015 eng d a0010-482500aGenome-wide identification and structure-function studies of proteases and protease inhibitors in cicer arietinum (chickpea)0 aGenomewide identification and structurefunction studies of prote aTHE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLANDbPERGAMON-ELSEVIER SCIENCE LTDcJAN a67-810 v563 a

Background: Proteases are a family of enzymes present in almost all living organisms. In plants they are involved in many biological processes requiring stress response in situations such as water deficiency, pathogen attack, maintaining protein content of the cell, programmed cell death, senescence, reproduction and many more. Similarly, protease inhibitors (PIs) are involved in various important functions like suppression of invasion by pathogenic nematodes, inhibition of spores-germination and mycelium growth of Alternaria alternata and response to wounding and fungal attack. As much as we know, no genome-wide study of proteases together with proteinaceous PIs is reported in any of the sequenced genomes till now. Methods: Phylogenetic studies and domain analysis of proteases were carried out to understand the molecular evolution as well as gene and protein features. Structural analysis was carried out to explore the binding mode and affinity of PIs for cognate proteases and prolyl oligopeptidase protease with inhibitor ligand. Results: In the study reported here, a significant number of proteases and PIs were identified in chickpea genome. The gene expression profiles of proteases and Pis in five different plant tissues revealed a differential expression pattern in more than one plant tissue. Molecular dynamics studies revealed the formation of stable complex owing to increased number of protein-ligand and inter and intramolecular protein-protein hydrogen bonds. Discussion: The genome-wide identification, characterization, evolutionary understanding, gene expression, and structural analysis of proteases and Pis provide a framework for future analysis when defining their roles in stress response and developing a more stress tolerant variety of chickpea. (C) 2014 Elsevier Ltd. All rights reserved.

10aDomain10aGene expression10aGenome analysis10aHomology modelling10aMolecular docking10amolecular dynamics simulation10aMotif10aOrthologs10aPhylogeny1 aSharma, Ranu1 aSuresh, C., G. uhttp://library.ncl.res.in/content/genome-wide-identification-and-structure-function-studies-proteases-and-protease-002535nas a2200205 4500008004100000022001400041245012100055210006900176260000800245520178100253653002102034653003402055653001302089653002402102653001502126100001802141700002202159700002102181856012702202 2019 eng d a0887-358500aMolecular basis of drug resistance in smoothened receptor: an in silico study of protein resistivity and specificity0 aMolecular basis of drug resistance in smoothened receptor an in  cOCT3 a

Smoothened (SMO) antagonist Vismodegib effectively inhibits the Hedgehog pathway in proliferating cancer cells. In early stage of treatment, Vismodegib exhibited promising outcomes to regress the tumors cells, but ultimately relapsed due to the drug resistive mutations in SMO mostly occurring before (primary mutations G497W) or after (acquired mutations D473H/Y) anti-SMO therapy. This study investigates the unprecedented insights of structural and functional mechanism hindering the binding of Vismodegib with sensitive and resistant mutant variants of SMO (SMOMut). Along with the basic dynamic understanding of Vismodegib-SMO complexes, network propagation theory based on heat diffusion principles is first time applied here to identify the modules of residues influenced by the individual mutations. The allosteric modulation by GLY497 residue in Vismodegib bound SMO wild-type (SMOWT) conformation depicts the interconnections of intermediate residues of SMO with the atom of Vismodegib and identify two important motifs (E-X-P-L) and (Q-A-N-V-T-I-G) mediating this allosteric regulation. In this study a novel computational framework based on the heat diffusion principle is also developed, which identify significant residues of allosteric site causing drug resistivity in SMOMut. This framework could also be useful for assessing the potential allosteric sites of different other proteins. Moreover, previously reported novel inhibitor ``ZINC12368305,'' which is proven to make an energetically favorable complex with SMOWT is chosen as a control sample to assess the impact of receptor mutation on its binding and subsequently identify the important factors that govern binding disparity between Vismodegib and ZINC12368305 bound SMOWT/Mut conformations.

10aallosteric sites10amolecular dynamics simulation10aMutation10asmoothened receptor10aVismodegib1 aSinha, Noopur1 aChowdhury, Saikat1 aSarkar, Ram, Rup uhttp://library.ncl.res.in/content/molecular-basis-drug-resistance-smoothened-receptor-silico-study-protein-resistivity-and02203nas a2200205 4500008004100000022001400041245014700055210006900202260000900271300001200280490000700292520144700299653003301746653003401779653001301813653001101826100002001837700001501857856012501872 2020 eng d a1539-445X00aGlass transition temperature of polybutadiene and polyisoprene from high temperature segmental relaxation correlation using molecular dynamics0 aGlass transition temperature of polybutadiene and polyisoprene f cJUL  a290-2960 v183 a

Predicting glass transition temperature for rubber and rubber composites is immensely important for tire industry for the development of products and fine-tune process conditions. Molecular dynamics simulation is been used to predict glass transition temperature as a function of molecular-level structural changes, e.g., composition (functional groups), topology, and polymerization. However, prediction of glass transition temperature within experimental error bar from molecular dynamics simulation is only possible from all atomistic description (model) of the system as united atom and coarse-grained models under-predict the values. Conventional way of calculation of glass transition temperature from density (or any other properties which show sharp transition)-temperature plots are computationally very demanding because of atomistic simulations and simulations below the glass transition point, i.e., in glassy state. Here we report a novel method for calculation of glass transition temperature using only segmental relaxation correlation functions calculated at higher temperatures, i.e., above glass transition temperature. We have presented a protocol here and shown for two polymeric systems polybutadiene and polyisoprene. We believe this method cuts the computational cost of predicting glass transition temperature by one-third and will be applicable for industrial applications for structure-property validations.

10aGlass transition temperature10amolecular dynamics simulation10aPolymers10arubber1 aSharma, Pragati1 aRoy, Sudip uhttp://library.ncl.res.in/content/glass-transition-temperature-polybutadiene-and-polyisoprene-high-temperature-segmental02399nas a2200217 4500008004100000022001400041245011200055210006900167260000800236300001200244490000700256520161500263653001301878653003401891653003101925653002401956653003301980100002302013700001502036856013002051 2023 eng d a0887-358500aGoverning dynamics and preferential binding of the AXH domain influence the aggregation pathway of Ataxin-10 aGoverning dynamics and preferential binding of the AXH domain in cMAR a380-3940 v913 a

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.

10aAtaxin-110amolecular dynamics simulation10aneurodegenerative diseases10aProtein aggregation10aprotein misfolding disorders1 aTammara, Vaishnavi1 aDas, Atanu uhttp://library.ncl.res.in/content/governing-dynamics-and-preferential-binding-axh-domain-influence-aggregation-pathway-ataxin02484nas a2200253 4500008004100000022001400041245020000055210006900255260000900324300001400333490000700347520152300354653002601877653001301903653002201916653003401938653001901972100002101991700002002012700002602032700002702058700002302085856012202108 2024 eng d a0739-110200aRepurposing phytochemicals of Citrullus colocynthis against maltase-glucoamylase using molecular docking, MMGBSA, MD simulation and linear regression to identify potential anti-diabetic compounds0 aRepurposing phytochemicals of Citrullus colocynthis against malt cJUL  a5197-52060 v423 a

Diabetes is a common lifestyle disorder found in populations of different age groups. Maltase-glucoamylase catalyses the release of the glucose molecule in the final enzymatic reaction of starch digestion; therefore, inhibition of maltase-glucoamylase is one of the approaches in the development of therapeutics for diabetes. Citrullus colocynthis is commonly recommended in Ayurveda for the treatment of diabetes. The current study applied a structure-based drug design approach to repurpose the phytochemicals of Citrullus colocynthis to identify potential inhibitors for maltase-glucoamylase. 70 phytochemicals of Citrullus colocynthis were screened against maltase-glucoamylase and top 5 molecules 8-p-hydroxybenzylisovitexin, isoorientin, cucurbitacin B, cucurbitacin E, and cucurbitacin I with significant binding energy of -10 kcal/mol, -9.9 kcal/mol, -9.6 kcal/mol, -9.2 kcal/mol, and -7.7 kcal/mol were identified. Furthermore, MMGBSA, pharmacokinetics properties and toxicity prediction were performed on the five identified molecules and top 3 molecules were selected for molecular dynamics (MD) simulation. It was observed from the structural flexibility and dynamic behaviour of the systems that conformational changes were noticed in the complexes as compared to its native state, which suggests that the 3 molecules, namely 8-p-hydroxybenzylisovitexin, isoorientin, and cucurbitacin I of Citrullus colocynthis may act as inhibitors for maltase-glucoamylase.Communicated by Ramaswamy H. Sarma

10aCitrullus colocynthis10aDiabetes10alinear regression10amolecular dynamics simulation10aphytochemicals1 aSahu, Parameswar1 aSahoo, Rosaleen1 aSahu, Abhishek, Kumar1 aSaluja, Sundeep, Singh1 aBehera, Banshidhar uhttp://library.ncl.res.in/content/repurposing-phytochemicals-citrullus-colocynthis-against-maltase-glucoamylase-using02558nas a2200265 4500008004100000022001400041245014200055210006900197260000900266300001100275490000800286520163300294653002301927653002201950653003401972653002102006653002602027100002002053700002102073700001902094700002202113700001702135700002002152856012002172 2024 eng d a0006-291X00aStructure of epoxide hydrolase 2 from Mangifera indica throws light on the substrate specificity determinants of plant epoxide hydrolases0 aStructure of epoxide hydrolase 2 from Mangifera indica throws li cNOV  a1504440 v7333 a

Epoxide hydrolases (EHs) are a group of ubiquitous enzymes that catalyze hydrolysis of chemically reactive epoxides to yield corresponding dihydrodiols. Despite extensive studies on EHs from different clades, generic rules governing their substrate specificity determinants have remained elusive. Here, we present structural, biochemical and molecular dynamics simulation studies on MiEH2, a plant epoxide hydrolase from Mangifera indica. Comparative structure-function analysis of nine homologs of MiEH2, which include a few AlphaFold structural models, show that the two conserved tyrosines (MiEH2Y152 and MiEH2Y232) from the lid domain dissect substrate binding tunnel into two halves, forming substrate-binding-pocket one (BP1) and two (BP2). This compartmentalization offers diverse binding modes to their substrates, as exemplified by the binding of smaller aromatic substrates, such as styrene oxide (SO). Docking and molecular dynamics simulations reveal that the linear epoxy fatty acid substrates predominantly occupy BP1, while the aromatic substrates can bind to either BP1 or BP2. Furthermore, SO preferentially binds to BP2, by stacking against catalytically important histidine (MiEH2H297) with the conserved lid tyrosines engaging its epoxide oxygen. Residue (MiEH2L263) next to the catalytic aspartate (MiEH2D262) modulates substrate binding modes. Thus, the divergent binding modes correlate with the differential affinities of the EHs for their substrates. Furthermore, long-range dynamical coupling between the lid and core domains critically influences substrate enantioselectivity in plant EHs.

10aEnantioselectivity10aEpoxide hydrolase10amolecular dynamics simulation10aRegioselectivity10aX-ray crystallography1 aBhoite, Ashwini1 aGaur, Neeraj, K.1 aPalange, Megha1 aKontham, Ravindar1 aGupta, Vidya1 aKulkarni, Kiran uhttp://library.ncl.res.in/content/structure-epoxide-hydrolase-2-mangifera-indica-throws-light-substrate-specificity