02428nas a2200277 4500008004100000022001400041245022800055210006900283260006800352300001400420490000700434520132000441653001401761653001801775653002301793653001501816653001801831653003601849653002301885100001801908700002501926700002101951700002801972700002302000856012702023 2006 eng d a0887-624X00aSynthesis, characterization, and molecular modeling studies of novel polyurethanes based on 2,2 '-[ethane-1,2-diylbis(nitrilomethylylidene)]diphenol and 2,2 '-[hexane-1,6-diylbis(nitrilomethylylidene)]diphenol hard segments0 aSynthesis characterization and molecular modeling studies of nov a111 RIVER ST, HOBOKEN, NJ 07030 USAbJOHN WILEY & SONS INCcOCT a6032-60460 v443 a

Novel polyurethanes (PUS) based on 2,2 `-[ethane-1,2-diylbis(nitrilomethylylidene)]diphenol and 2,2 `-[hexane-1,6-diylbis(nitrilomethylylidene)]diphenol as hard segments containing four aromatic diisocyanates (4,4 `-diphenylmethane diisocyanate, toluene 2,4-diisocyanate, isophorone diisocyanate, and hexamethylene diisocyanate) have been prepared. Fourier transform infrared, UV spectrophotometry, fluorescence spectroscopy, H-1 NMR and C-13 NMR spectroscopy, thermogravimetric analysis, and differential thermal analysis have been used to determine the structural characterization and thermal properties of the segmented PUS. All the PUS contain domains of both semicrystalline and amorphous structures, as indicated by X-ray diffraction. The acoustic properties have been calculated with the group contribution method. Molecular dynamics simulations have been performed on all the PUS to estimate the cohesive energy density and solubility parameter values, which compare well with the values calculated with the group contribution method. Furthermore, the simulation protocols have been applied to the PUS to produce X-ray diffraction plots to determine the phase morphology of the PUS. The surface properties of the PUS have been estimated from the simulation protocols. (c) 2006 Wiley Periodicals, Inc.

10aamorphous10ahard segments10amolecular dynamics10aMorphology10apolyurethanes10aSchiff base containing polymers10aThermal properties1 aRaghu, A., V.1 aGadaginamath, G., S.1 aJawalkar, S., S.1 aHalligudi, Shivaraj, B.1 aAminabhavi, T., A. uhttp://library.ncl.res.in/content/synthesis-characterization-and-molecular-modeling-studies-novel-polyurethanes-based-22-102196nas a2200253 4500008004100000022001400041245013900055210006900194260008600263300001400349490000700363520124800370653002001618653002501638653002101663653001701684653002301701653001801724653001901742653001201761100002601773700002301799856012001822 2012 eng d a0022-234800aPrediction of structure and energy of trans-1,4-polybutadiene glassy surface by atomistic simulations of free-standing ultrathin films0 aPrediction of structure and energy of trans14polybutadiene glass a325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USAbTAYLOR & FRANCIS INCcMAR a2201-22210 v513 a

Atomistic modeling of amorphous trans-1,4-polybutadiene (TPBD), using molecular mechanics and molecular dynamics (MD) simulations, is performed to generate three-dimensionally periodic bulk and two-dimensionally periodic thin film condensed phases. The condensed structures are constructed using multiple polymer chains. Structural and energetic relaxations and sampling of properties are performed using MD in the canonical ensemble (NVT) by a procedure that relieves local high-energy spots and brings the system to realistic thermodynamic states. The calculated surface energy for TPBD, 30.72 erg/cm(2), is in excellent agreement with the reported experimental value of 31 erg/cm(2). The structure of the surface layers is probed in terms of the atomic mass density variations, bond-bond orientation function profiles, and the distribution of the dihedral angles about the rotatable backbone bonds. The thickness of the surface layer over which the density varies smoothly but rapidly is found to be approximately 15 angstrom. The level of agreement of the calculated surface energy with the experimental value is superior in comparison to previous investigations in the literature using the atomistic approach for flexible polymers.

10a4-polybutadiene10aatomistic simulation10abond-orientation10aConformation10amolecular dynamics10apolymer glass10asurface energy10atrans-11 aIjantkar, Ashwini, S.1 aNatarajan, Upendra uhttp://library.ncl.res.in/content/prediction-structure-and-energy-trans-14-polybutadiene-glassy-surface-atomistic-002328nas a2200301 4500008004100000022001400041245003300055210003200088260008000120300001400200490000800214520144900222653001401671653002501685653001901710653002301729653002001752100001801772700001601790700001701806700002001823700003201843700002101875700002401896700001701920700002001937856006901957 2012 eng d a0027-842400aRapid self-healing hydrogels0 aRapid selfhealing hydrogels a2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USAbNATL ACAD SCIENCEScMAR a4383-43880 v1093 a

Synthetic materials that are capable of autonomous healing upon damage are being developed at a rapid pace because of their many potential applications. Despite these advancements, achieving self-healing in permanently cross-linked hydrogels has remained elusive because of the presence of water and irreversible cross-links. Here, we demonstrate that permanently cross-linked hydrogels can be engineered to exhibit self-healing in an aqueous environment. We achieve this feature by arming the hydrogel network with flexible-pendant side chains carrying an optimal balance of hydrophilic and hydrophobic moieties that allows the side chains to mediate hydrogen bonds across the hydrogel interfaces with minimal steric hindrance and hydrophobic collapse. The self-healing reported here is rapid, occurring within seconds of the insertion of a crack into the hydrogel or juxtaposition of two separate hydrogel pieces. The healing is reversible and can be switched on and off via changes in pH, allowing external control over the healing process. Moreover, the hydrogels can sustain multiple cycles of healing and separation without compromising their mechanical properties and healing kinetics. Beyond revealing how secondary interactions could be harnessed to introduce new functions to chemically crosslinked polymeric systems, we also demonstrate various potential applications of such easy-to-synthesize, smart, self-healing hydrogels.

10aadhesives10abiomimetic materials10aHydrophobicity10amolecular dynamics10asmart materials1 aPhadke, Ameya1 aZhang, Chao1 aArman, Bedri1 aHsu, Cheng-Chih1 aMashelkar, Raghunath, Anant1 aLele, Ashish, K.1 aTauber, Michael, J.1 aArya, Gaurav1 aVarghese, Shyni uhttp://library.ncl.res.in/content/rapid-self-healing-hydrogels-001869nas a2200229 4500008004100000022001400041245012800055210006900183260005700252300001200309490000700321520101000328653002601338653001801364653002301382653003401405100001601439700002001455700001501475700002301490856012601513 2013 eng d a1610-294000aCharacterization of the structures and dynamics of phosphoric acid doped benzimidazole mixtures: a molecular dynamics study0 aCharacterization of the structures and dynamics of phosphoric ac a233 SPRING ST, NEW YORK, NY 10013 USAbSPRINGERcJAN a109-1180 v193 a

Benzimidazole-based polymer membranes like poly(2,5-benzimidazole) (ABPBI) doped with phosphoric acid (PA) are electrolytes that exhibit high proton conductivity in fuel cells at elevated temperatures. The benzimidazole (BI) moiety is an important constituent of these membranes, so the present work was performed in order to achieve a molecular understanding of the BI-PA interactions in the presence of varying levels of the PA dopant, using classical molecular dynamics (MD) simulations. The various hydrogen-bonding interactions, as characterized based on structural properties and hydrogen-bond lifetime calculations, show that both BI and PA molecules exhibit dual proton-acceptor/donor functionality. An examination of diffusion coefficients showed that the diffusion of BI decreases with increasing PA uptake, whereas the diffusion of PA slightly increases. The hydrogen-bond lifetime calculations pointed to the existence of competitive hydrogen bonding between various sites in BI and PA.

10aDiffusion coefficient10aHydrogen bond10amolecular dynamics10aRadial distribution functions1 aMore, Minal1 aPahari, Swagata1 aRoy, Sudip1 aVenkatnathan, Arun uhttp://library.ncl.res.in/content/characterization-structures-and-dynamics-phosphoric-acid-doped-benzimidazole-mixtures-002386nas a2200277 4500008004100000022001400041245015700055210006900212260008600281300001200367490000700379520129800386653002201684653002301706653003801729653003301767100002201800700002301822700002101845700002301866700002501889700002201914700002701936700002201963856012301985 2016 eng d a0739-110200aMolecular interaction of selected phytochemicals under the charged environment of Plasmodium falciparum chloroquine resistance transporter (PfCRT) model0 aMolecular interaction of selected phytochemicals under the charg a530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USAbTAYLOR & FRANCIS INCcFEB a290-3030 v343 a

Phytochemicals of Catharanthus roseus Linn. and Tylophora indica have been known for their inhibition of malarial parasite, Plasmodium falciparum in cell culture. Resistance to chloroquine (CQ), a widely used antimalarial drug, is due to the CQ resistance transporter (CRT) system. The present study deals with computational modeling of Plasmodium falciparum chloroquine resistance transporter (PfCRT) protein and development of charged environment to mimic a condition of resistance. The model of PfCRT was developed using Protein homology/analogy engine (PHYRE ver 0.2) and was validated based on the results obtained using PSI-PRED. Subsequently, molecular interactions of selected phytochemicals extracted from C. roseus Linn. and T. indica were studied using multiple-iterated genetic algorithm-based docking protocol in order to investigate the translocation of these legends across the PfCRT protein. Further, molecular dynamics studies exhibiting interaction energy estimates of these compounds within the active site of the protein showed that compounds are more selective toward PfCRT. Clusters of conformations with the free energy of binding were estimated which clearly demonstrated the potential channel and by this means the translocation across the PfCRT is anticipated.

10ahomology modeling10amolecular dynamics10aPlasmodium falciparum chloroquine10aresistance transporter model1 aPatel, Saumya, K.1 aKhedkar, Vijay, M.1 aJha, Prakash, C.1 aJasrai, Yogesh, T.1 aPandya, Himanshu, A.1 aGeorge, Linz-Buoy1 aHighland, Hyacinth, N.1 aSkelton, Adam, A. uhttp://library.ncl.res.in/content/molecular-interaction-selected-phytochemicals-under-charged-environment-plasmodium-002451nas a2200265 4500008004100000022001400041245015600055210006900211260009500280300001000375490000800385520139300393653002201786653002801808653002301836653001601859653002801875100002901903700002601932700001801958700002001976700003401996700002602030856012902056 2016 eng d a1047-847700aStructural analysis of a penicillin V acylase from pectobacterium atrosepticum confirms the importance of two Trp residues for activity and specificity0 aStructural analysis of a penicillin V acylase from pectobacteriu a525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USAbACADEMIC PRESS INC ELSEVIER SCIENCEcFEB a85-940 v1933 a

Penicillin V acylases (PVA) catalyze the deacylation of the beta-lactam antibiotic phenoxymethylpenicillin (Pen V). They are members of the Ntn hydrolase family and possess an N-terminal cysteine as the main catalytic nucleophile residue. They form the evolutionarily related cholylglycine hydrolase (CGH) group which includes bile salt hydrolases (BSH) responsible for bile deconjugation. Even though a few PVA and BSH structures have been reported, no structure of a functional PVA from Gram-negative bacteria is available. Here, we report the crystal structure of a highly active PVA from Gram-negative Pectobacterium atrosepticum (PaPVA) at 2.5 angstrom resolution. Structural comparison with PVAs from Gram-positive bacteria revealed that PaPVA had a distinctive tetrameric structure and active site organization. In addition, mutagenesis of key active site residues and biochemical characterization of the resultant variants elucidated the role of these residues in substrate binding and catalysis. The importance of residue Trp23 and Trp87 side chains in binding and correct positioning of Pen V by PVAs was confirmed using mutagenesis and substrate docking with a 15 ns molecular dynamics simulation. These results establish the unique nature of Gram-negative CGHs and necessitate further research about their substrate spectrum. (C) 2015 Elsevier Inc. All rights reserved.

10aAromatic stacking10aCholylglycine hydrolase10amolecular dynamics10aMutagenesis10aOligomeric interactions1 aAvinash, Vellore, Sunder1 aPanigrahi, Priyabrata1 aChand, Deepak1 aPundle, Archana1 aSuresh, Cheravakattu, Gopalan1 aRamasamy, Sureshkumar uhttp://library.ncl.res.in/content/structural-analysis-penicillin-v-acylase-pectobacterium-atrosepticum-confirms-importance-003018nas a2200265 4500008004100000022001300041245014800054210006900202260000800271300001200279490000900291520209300300653002902393653002402422653002302446653001602469653002602485653002602511100001402537700001802551700001702569700001702586700001902603856013002622 2018 eng d a1570963900aStructure and function of a highly active Bile Salt Hydrolase (BSH) from Enterococcus faecalis and post-translational processing of BSH enzymes0 aStructure and function of a highly active Bile Salt Hydrolase BS cJAN a507-5180 v18663 aBile Salt Hydrolase (BSH), a member of Cholylglycine hydrolase family, catalyzes the de-conjugation of bile acids and is evolutionarily related to penicillin V acylase (PVA) that hydrolyses a different substrate such as penicillin V. We report the three-dimensional structure of a BSH enzyme from the Gram-positive bacteria Enterococcus faecalis (EfBSH) which has manifold higher hydrolase activity compared to other known BSHs and displays unique allosteric catalytic property. The structural analysis revealed reduced secondary structure content compared to other known BSH structures, particularly devoid of an anti-parallel β-sheet in the assembly loop and part of a β-strand is converted to increase the length of a substrate binding loop 2. The analysis of the substrate binding pocket showed reduced volume owing to altered loop conformations and increased hydrophobicity contributed by a higher ratio of hydrophobic to hydrophilic groups present. The aromatic residues F18, Y20 and F65 participate in substrate binding. Thus, their mutation affects enzyme activity. Docking and Molecular Dynamics simulation studies showed effective polar complementarity present for the three hydroxyl (-OH) groups of GCA substrate in the binding site contributing to higher substrate specificity and efficient catalysis. These are unique features characteristics of this BSH enzyme and thought to contribute to its higher activity and specificity towards bile salts as well as allosteric effects. Further, mechanism of autocatalytic processing of Cholylglycine Hydrolases by the excision of an N-terminal Pre-peptide was examined by inserting different N-terminal pre-peptides in EfBSH sequence. The results suggest that two serine residues next to nucleophile cysteine are essential for autocalytic processing to remove precursor peptide. Since pre-peptide is absent in EfBSH the mutation of these serines is tolerated. This suggests that an evolution-mediated subordination of the pre-peptide excision site resulted in loss of pre-peptide in EfBSH and other related Cholylglycine hydrolases.10aautocatalytic processing10aBile salt hydrolase10amolecular dynamics10aMutagenesis10aPolar complementarity10aX-ray crystallography1 aChand, D.1 aPanigrahi, P.1 aVarshney, N.1 aRamasamy, S.1 aSuresh, C., G. uhttp://library.ncl.res.in/content/structure-and-function-highly-active-bile-salt-hydrolase-bsh-enterococcus-faecalis-and-post02199nas a2200253 4500008004100000022001400041245010400055210006900159260000800228300001200236490000800248520136000256653003201616653003101648653000901679653002301688653002101711653000801732100002101740700002101761700002001782700001801802856012501820 2019 eng d a0022-263100aDifferential dynamics underlying the Gln27Glu population variant of the beta(2)-adrenergic receptor0 aDifferential dynamics underlying the Gln27Glu population variant cOCT a499-5070 v2523 a

The beta (2)-adrenergic receptor (beta (2)AR) is a membrane-bound G-protein-coupled receptor and an important drug target for asthma. Clinical studies report that the population variant Gln27Glu is associated with a differential response to common asthma drugs, such as albuterol, isoproterenol and terbutaline. Interestingly, the 27th amino acid is positioned on the N-terminal region that is the most flexible and consequently the least studied part of the receptor. In this study, we probe the molecular origin of the differential drug binding by performing structural modeling and simulations of the wild-type (Gln) and variant (Glu) receptors followed by ensemble docking with the ligands, albuterol, isoproterenol and terbutaline. In line with clinical studies, the ligands were observed to interact preferentially with the Glu variant. Our results indicate that the Glu residue at the 27th position perturbs the network of electrostatic interactions that connects the N-terminal region to the binding site in the wild-type receptor. As a result, the Glu variant is observed to bind better to the three ligands tested in this study. Our study provides a structural basis to explain the variable drug response associated with the 27th position polymorphism in the beta (2)AR and is a starting step to identify genotype-specific therapeutics.

10abeta(2)-Adrenergic receptor10aG-protein-coupled receptor10aGPCR10amolecular dynamics10aPharmacogenetics10aSNP1 aBhosale, Sumedha1 aNikte, Siddhanta1 aSengupta, Durba1 aJoshi, Manali uhttp://library.ncl.res.in/content/differential-dynamics-underlying-gln27glu-population-variant-beta2-adrenergic-receptor02241nas a2200241 4500008004100000022001400041245013700055210006900192260000900261300001200270490000800282520138800290653002301678653002401701653002801725653003401753653002601787100001701813700000501830700002001835700002001855856012401875 2021 eng d a0006-291X00aDynamic coupling analysis on plant sesquiterpene synthases provides leads for the identification of product specificity determinants0 aDynamic coupling analysis on plant sesquiterpene synthases provi cJAN  a107-1140 v5363 a

Sesquiterpene synthases catalyse cyclisation of farnesyl pyrophosphate to produce diverse sesquiterpenes. Despite utilising the same substrate and exhibiting significant sequence and structural homology, these enzymes form different products. Previous efforts were based on identifying the effect of divergent residues present at the catalytic binding pocket on the product specificity of these enzymes. However, the rationales deduced for the product specificity from these studies were not generic enough to be applicable to other phylogenetically distant members of this family. To address this problem, we have developed a novel approach combining sequence, structural and dynamical information of plant sesquiterpene synthases (SSQs) to predict product modulating residues (PMRs). We tested this approach on the SSQs with known PMRs and also on sesquisabinene synthase 1 (SaSQS1), a SSQ from Indian sandalwood. Our results show that the dynamical sectors of SSQs obtained from molecular dynamics simulation and their hydrophobicity and vicinity indices together provide leads for the identification of PMRs. The efficacy of the technique was tested on SaSQS1 using mutagenesis. To the best of our knowledge, this is a first technique of this kind which provides cues on PMRs of SSQs, with divergent phylogenetic relationship. (C) 2020 Elsevier Inc. All rights reserved.

10amolecular dynamics10aProduct specificity10aSesquiterpene synthases10aStatistical coupling analysis10aX-ray crystallography1 aSingh, Sneha1 a1 aSengupta, Durba1 aKulkarni, Kiran uhttp://library.ncl.res.in/content/dynamic-coupling-analysis-plant-sesquiterpene-synthases-provides-leads-identification02290nas a2200265 4500008004100000022001400041245012300055210006900178260000800247300001100255490000900266520140300275653003201678653003101710653000901741653002301750653002101773653000801794100002101802700001901823700001901842700001801861700002001879856012501899 2021 eng d a1570-963900aLoss of a water-mediated network results in reduced agonist affinity in a beta(2)-adrenergic receptor clinical variant0 aLoss of a watermediated network results in reduced agonist affin cAPR a1406050 v18693 a

The beta(2)-adrenergic receptor (beta(2)AR) is a member of the G protein-coupled receptor (GPCR) family that is an important drug target for asthma and COPD. Clinical studies coupled with biochemical data have identified a critical receptor variant, Thr164Ile, to have a reduced response to agonist-based therapy, although the molecular mechanism underlying this seemingly ``non-deleterious'' substitution is not clear. Here, we couple molecular dynamics simulations with network analysis and free-energy calculations to identify the molecular determinants underlying the differential drug response. We are able to identify hydration sites in the transmembrane domain that are essential to maintain the integrity of the binding site but are absent in the variant. The loss of these hydration sites in the variant correlates with perturbations in the intra-protein interaction network and rearrangements in the orthosteric ligand binding site. In conjunction, we observe an altered binding and reduced free energy of a series of agonists, in line with experimental trends. Our work identifies a functional allosteric pathway connected by specific hydration sites in beta(2)AR that has not been reported before and provides insight into water-mediated networks in GPCRs in general. Overall, the work is one of the first step towards developing variant-specific potent and selective agonists.

10abeta(2)-Adrenergic receptor10aG protein coupled receptor10aGPCR10amolecular dynamics10aPharmacogenetics10aSNP1 aNikte, Siddhanta1 aSonar, Krushna1 aTandale, Aditi1 aJoshi, Manali1 aSengupta, Durba uhttp://library.ncl.res.in/content/loss-water-mediated-network-results-reduced-agonist-affinity-beta2-adrenergic-receptor02261nas a2200241 4500008004100000022001400041245009500055210006900150260000800219490000800227520149500235653001201730653002501742653001701767653002301784653002401807653001401831100001701845700000501862700002201867700001801889856011201907 2021 eng d a0022-263100aMolecular characterization of the beta(2)-like octopamine receptor of helicoverpa armigera0 aMolecular characterization of the beta2like octopamine receptor  cJUN0 v2543 a

Helicoverpa armigera is a devastating polyphagous and cosmopolitan crop pest. There are reports of this insect being resistant to a variety of pesticides raising concern worldwide. The Octopamine (OA) binding beta(2)-like receptor (OAR), a GPCR, is widely distributed in the nervous system of the insect and plays essential roles in the physiology and development and thus is an important target for insecticides. Yet, the molecular characterization of the H. armigera OAR (HarmOAR) and rational design of compounds based on this receptor is lacking. As a first step, we performed multiple sequence alignment of all insect OARs, which revealed that the sequences contained all conserved class A GPCR motifs. Phylogenetic studies showed clade-specific variations in the protein sequences primarily arising owing to differences in the ICL3 loop region. Further, a structural model of HarmOAR was built using the inactive human beta(2)AR as a template. 0.9 mu s atomistic simulations revealed conserved inter helical contacts and water molecules of HarmOAR. The detailed binding of octopamine was studied using molecular docking and 0.3 mu s atomistic simulations. Twenty-two insecticides active against octopamine receptors of other insects were compiled and docked to HarmOAR followed by rescoring with binding free energies to prioritize them for H. armigera. Our study suggests alpha-terpineol to be a good candidate as an insecticide or insect repellent for Helicoverpa armigera.

10adocking10aHelicoverpa armigera10aInsecticides10amolecular dynamics10aOctopamine receptor10aPhylogeny1 aGujar, Nidhi1 a1 aJoshi, Rakesh, S.1 aJoshi, Manali uhttp://library.ncl.res.in/content/molecular-characterization-beta2-octopamine-receptor-helicoverpa-armigera02185nas a2200265 4500008004100000022001400041245008200055210007000137260000800207490000700215520129400222653002501516653002801541653002601569653002301595653001501618100002201633700003501655700001901690700001801709700002201727700002501749700002801774856011701802 2023 eng d a1612-187200aDiscovery of SARS-CoV-2 inhibitors featuring novel histidine α-nitrile motif0 aDiscovery of SARSCoV2 inhibitors featuring novel histidine αnitr cDEC0 v203 a

As COVID-19 infection caused severe public health concerns recently, the development of novel antivirals has become the need of the hour. Main protease (Mpro) has been an attractive target for antiviral drugs since it plays a vital role in polyprotein processing and virus maturation. Herein we report the discovery of a novel class of inhibitors against the SARS-CoV-2, bearing histidine alpha-nitrile motif embedded on a simple dipeptide framework. In-vitro and in-silico studies revealed that the histidine alpha-nitrile motif envisioned to target the Mpro contributes to the inhibitory activity. Among a series of dipeptides synthesized featuring this novel structural motif, some dipeptides displayed strong viral reduction (EC50=0.48 mu M) with a high selectivity index, SI>454.54. These compounds also exhibit strong binding energies in the range of -28.7 to -34.2 Kcal/mol. The simple dipeptide structural framework, amenable to quick structural variations, coupled with ease of synthesis from readily available commercial starting materials are the major attractive features of this novel class of SARS-CoV-2 inhibitors. The histidine alpha-nitrile dipeptides raise the hope of discovering potent drug candidates based on this motif to fight the dreaded SARS-CoV-2.

10adipeptide inhibitors10ahistidine alpha-nitrile10aM-pro (main protease)10amolecular dynamics10aSARS-CoV-21 aGone, Nilu, Vijay1 aEnayathullah, Mohammed, Ghalib1 aThomas, Jessie1 aRathee, Parth1 aPrabhakar, Rajeev1 aBokara, Kiran, Kumar1 aSanjayan, Gangadhar, J. uhttp://library.ncl.res.in/content/discovery-sars-cov-2-inhibitors-featuring-novel-histidine-%CE%B1-nitrile-motif02421nas a2200229 4500008004100000022001400041245008700055210006900142260000800211300001400219490000700233520167000240653002301910653001501933653002301948100002001971700002101991700002102012700001702033700002302050856011802073 2023 eng d a0739-110200aRepurposing small molecules of Tephrosia purpurea against SARS-CoV-2 main protease0 aRepurposing small molecules of Tephrosia purpurea against SARSCo cSEP a6822-68330 v413 a

Coronavirus infection is a communicable disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which emerged as a global pandemic with deteriorating effect on the world's population. Main protease (M-pro) of SARS-CoV-2 plays a significant role in the viral replication, transcription and disease propagation as well as a potential candidate for drug discovery and development for COVID-19 infection. The current study employed state of art structure-based drug discovery to decipher the role of phytochemicals of Tephrosia purpurea against M-pro. Tephrosia purpurea is being used as a traditional medicinal plant for the treatment of cough, breathlessness and fever as per the Indian Materia Medica. Screening of the phytochemicals of Tephrosia purpurea against M-pro was performed using molecular docking approach to identify the top 5 hits (+)-tephrorin B, deguelin, vitamin p, lanceolarin and 3beta-hydroxy-20(29)-lupene with binding energy of -8.4, -8.1, -8.0, -7.8, and -7.8 kcal/mol, respectively. Furthermore, identified top 5 hits were subjected to drug-likeness and toxicity prediction as well as MM-GBSA calculation. Out of the five molecules four molecules were predicted not to comprise any mutagenic and carcinogenic effects. Top two molecules based on the drug-likeness properties for oral bio-availability were further analysed by molecular dynamics simulation at 100 ns timescale. It was observed from the dynamic behaviour of the two complexes that the addition of these molecules changed the conformation and stability of the apo protein; thus may act as inhibitors for M-pro. Communicated by Ramaswamy H. Sarma

10amolecular dynamics10aSARS-CoV-210aTephrosia purpurea1 aSahoo, Rosaleen1 aSahu, Parameswar1 aSwargam, Sandeep1 aKumari, Indu1 aBehera, Banshidhar uhttp://library.ncl.res.in/content/repurposing-small-molecules-tephrosia-purpurea-against-sars-cov-2-main-protease02171nas a2200265 4500008004100000022001400041245007500055210006900130260000900199300001100208490000800219520135600227653001101583653001201594653003101606653002301637653001801660653002001678100002101698700002001719700001901739700002401758700002001782856010301802 2023 eng d a0167-732200aSurface-induced demixing of self-assembled isomeric mixtures of citral0 aSurfaceinduced demixing of selfassembled isomeric mixtures of ci cJUL  a1218030 v3813 a

The self-assembly of organic molecules and their interactions with metal surfaces have been of considerable interest, both for developing novel functional materials and for understanding fundamental design principles of nanostructures. In this study, we investigate the solution and surface-induced self-assembly of two stereoisomers of citral molecules (geranial and neral) using atomistic molecular dynamics simulations. We demonstrate that the morphology of the aggregates in water is concentration dependent (ranging from distorted spherical to slab-like aggregates) but independent of isomer effects. The isomeric mixtures of citral indicate homogeneous mixing based on differential density maps and high values of Shannon entropy. Interestingly, surface-confinement of citral aggregates on a Cu(111) surface leads to phase segregation and demixing of the two isomers that is more apparent in the surface-bound monolayer in comparison to the adjacent layers. Positional ordering and formation of domains are observed over a series of isomeric citral mixtures with varying compositions, as indicated by high differential density and low values of Shannon entropy. Our work provides new insights into molecular self-assembly of organic molecules in nanostructures and metal-organic overlayers.(c) 2023 Elsevier B.V. All rights reserved.

10aCitral10aIsomers10aMetal-organic interactions10amolecular dynamics10aSelf-assembly10aShannon entropy1 aSaraf, Deepashri1 aPrakash, Shikha1 aPinjari, Aadil1 aPujari, Bhalchandra1 aSengupta, Durba uhttp://library.ncl.res.in/content/surface-induced-demixing-self-assembled-isomeric-mixtures-citral02301nas a2200229 4500008004100000022001400041245012500055210006900180260000800249490000700257520147900264653001901743653002201762653002001784653003601804653002301840100001701863700002601880700002401906700001701930856012401947 2024 eng d a1439-423500aSize and morphology dependent activity of Cu clusters for CO2 activation and reduction: a first principles investigation0 aSize and morphology dependent activity of Cu clusters for CO2 ac cDEC0 v253 a

Various Cu-based materials in diverse forms have been investigated as efficient catalysts for electrochemical reduction of CO2; however, they suffer from issues such as higher over potential and poor selectivity. The activity and selectivity of CO2 electro reduction have been shown to change significantly when the surface morphology (steps, kinks, and edges) of these catalysts is altered. In light of this, size and morphology dependent activity of selected copper clusters, Cun (n=2-20) have been evaluated for the activation and reduction of CO2 molecule. The phase-space of these copper clusters is rich in conformations of distinct morphologies starting from planar, 2D geometries to prolate-shaped geometries and also high-symmetry structures. The binding efficiency and the activation of CO2 are highest for medium sized clusters (n=9-17) with prolate-morphologies as compared to small or larger sized CunCO(2) clusters that are existing mainly as planar (triangular, tetragonal etc.) or highly-symmetric geometries (icosahedron, capped-icosahedron etc.), respectively. The best performing (prolate-shaped) CunCO2 conformations are quite fluxional and also they are thermally stable, as demonstrated by the molecular dynamics simulations. Furthermore, on these CunCO(2) conformations, the step-by-step hydrogenation pathways of CO2 to produce value-added products like methanol, formic acid, and methane are exceptionally favorable and energy-efficient.

10aCO2 activation10aCO2 hydrogenation10aCopper clusters10aDensity Functional Theory (DFT)10amolecular dynamics1 aAmin, Seerat1 aKrishnamurty, Sailaja1 aDar, Manzoor, Ahmad1 aJoshi, Krati uhttp://library.ncl.res.in/content/size-and-morphology-dependent-activity-cu-clusters-co2-activation-and-reduction-first