Utility of Cell Saver in Trauma Compared to Cardiac Surgery.

While reperfusion of autologous blood using the Cellsaver (CS) device is routine in cardiothoracic surgery, there is a paucity of evidence-based literature regarding its use in trauma. Utility of CS was compared in these two distinct populations at a Level 1 trauma center from 2017 to 2022. CS was successfully used in 97% and 74% of cardiac and trauma cases, respectively. The proportion of blood requirements provided by CS, compared to allogenic transfusion, was also significantly higher in cardiac surgery. However, there was still net benefit for CS in trauma surgery, with median salvaged transfusion volume of one unit, in both general & orthopedic trauma. Therefore, in centers where the cost of setting up CS, both in terms of equipment and personnel, is less than the cost of one unit of blood from blood bank, use of CS in trauma operations should be considered.

Molecular modelling of coat protein of the Groundnut bud necrosis tospovirus and its binding with Squalene as an antiviral agent: In vitro and in silico docking investigations.

Bud blight disease caused by groundnut bud necrosis virus (GBNV) is a serious constraint in the cultivation of agricultural crops such as legumes, tomato, chilies, potato, cotton etc. Owing to the significant damage caused by GBNV, an attempt was made to identify suitable organic antiviral agents through molecular modelling of the nucleocapsid Coat Protein of GBNV; molecular docking and molecular dynamics that disclosed the interaction of the ligands viz., Squalene and Ganoderic acid-A with coat protein of GBNV. Invitro inhibitory effect of Squalene and Ganoderic acid-A was examined in comparison with different concentrations, against GBNV in cowpea plants under glasshouse condition. The different concentrations of Squalene (50, 100, 150, 250 and 500 ppm) tested in vitro resulted in reduction of lesion numbers (1.69 cm2) as well as reduced virus titre in co-inoculation spray. The present study suggests the antiviral activity of Squalene by effectively fitting into binding site of coat protein of GBNV with favourable hydrophilic as well as strong hydrophobic interactions thereby challenging and blocking the binding of viral replication RNA with coat protein and propagation. The present organic antiviral molecules will be helpful in development of suitable eco-friendly formulations to mitigate GBNV infection disease in plants.

Statistical optimization of textile dye effluent adsorption by Gracilaria edulis using Plackett-Burman design and response surface methodology.

Statistical optimization models were employed to optimize the adsorption of textile dye effluent onto Gracilaria edulis. Significant factors responsible for adsorption were determined using Plackett-Burman design (PBD) and were time, pH, and dye concentration. Box-Behnken (BB) design was used for further optimization. The predicted and the experimental values were found to be in good agreement, the coefficient of determination value 0.9935 and adjusted coefficient of determination value 0.9818 indicated that the model was significant. The results of predicted response optimization showed that maximum decolorization could be attained with time 131.51 min, pH 7.48, and dye concentration 23.13%. The model was validated experimentally with 92.65% decolorization efficiency. The experiment was confirmed using Fourier transform infrared spectroscopy (FTIR), high-resolution scanning electron microscope coupled with energy dispersive X-ray analysis (HR-SEM-EDX), X-ray diffraction spectrometry (XRD) and Brunauer-Emmett-Teller (BET) surface area and pore size analysis techniques. Desorption studies at various pH (2-14) were performed and a maximum of 23% of the dye was recovered from the adsorbed biomass.

Antiviral activity of basidiomycetous fungi against Groundnut bud necrosis virus in tomato.

Tomato is an important vegetable crop which is severely affected by Groundnut bud necrosis virus (GBNV). Until now effective antiviral agents have not been reported for the management of necrosis disease caused by GBNV. Therefore, a study was undertaken to manage the necrosis disease caused by GBNV using culture filtrate of basidiomycetous fungi viz., Coprinopsiscinerea, Ganoderma lucidum and Lentinula edodes. In vitro studies were conducted in the indicator host cowpea and primary host tomato in glasshouse under insect proof condition; co-inoculation spraying of culture filtrate of Ganoderma lucidum at 0.1% concentration reduced the lesion numbers and inhibited the virus population build-up when compared to inoculated control in the indicator host cowpea upto 77.83%. DAC-ELISA test was performed to quantify the virus titre, indicated reduced virus titre in co- inoculation spray of culture filtrate of G. lucidum treated cowpea with OD value 0.17 ± 0.01 at 405 nm and in tomato plants 0.14 ± 0.01 respectively. The viral copy numbers were quantified by qPCR. About 2.0 × 101 viral copy numbers were observed in tomato plants treated with G. lucidum (co-inoculation) which was lesser than untreated inoculated control plants (2.4 × 108). In order to identify the antiviral properties of G. lucidum, GCMS analysis was carried out and we found the triterpenoid compound Squalene. This is the first study to analyse and confirm the antiviral activity of G. lucidum against a plant virus.

Molecular dynamics investigations for the prediction of molecular interaction of cauliflower mosaic virus transmission helper component protein complex with Myzus persicae stylet's cuticular protein and its docking studies with annosquamosin-A encapsulated in nano-porous Silica.

Large numbers of bioactive natural products from plant species such as alkaloids, phenolics, terpenoids etc. are remaining unexplored for their potential as plant protective agents as inhibitors for viral and other pathogenic infections of plant. Myzus aphids are important plant pests and vectors for several plant viruses. Cauliflower mosaic virus (CaMV) belongs to the plant virus family Caulimoviridae which is transmitted "non-circulative" from plant to plant through an interaction with aphid insect vectors. This viral transmission process most likely involves a protein-protein binding interaction between aphid stylet receptor cuticular protein and viral proteins namely, CaMV aphid transmission Helper Component protein and virion associated protein. Aphid stylets are made of cuticle and little is known about the structure of cuticle protein of this insect group. The present study reports the molecular modeling of the structures of Myzus persicae aphid stylet's cuticular protein (MpsCP) and cauliflower mosaic virus aphid transmission Helper component protein (CaMV HCP). Protein-protein docking studies and molecular dynamics simulations are performed to establish the mode of binding of MpsCP with CaMV HCP. Molecular docking and molecular dynamics investigations of terpenoids Annosquamosin-A from Annona squamosa complex with CaMV transmitting aphid M. persicae stylet's cuticular protein revealed their means of interaction perhaps relates to restrain viral binding and transmission. QM/MM optimization of mesoporous silica nanopores composite with Annosquamosin-A for smart and safe delivery of bioactive is carried out to study their electronic parameters such as heat of formation, total energy, electronic energy, Ionization potential, Highest Occupied Molecular Orbital, Lowest Un-occupied Molecular Orbital and energy gaps.

SVMRFE based approach for prediction of most discriminatory gene target for type II diabetes.

Type II diabetes is a chronic condition that affects the way our body metabolizes sugar. The body's important source of fuel is now becoming a chronic disease all over the world. It is now very necessary to identify the new potential targets for the drugs which not only control the disease but also can treat it. Support vector machines are the classifier which has a potential to make a classification of the discriminatory genes and non-discriminatory genes. SVMRFE a modification of SVM ranks the genes based on their discriminatory power and eliminate the genes which are not involved in causing the disease. A gene regulatory network has been formed with the top ranked coding genes to identify their role in causing diabetes. To further validate the results pathway study was performed to identify the involvement of the coding genes in type II diabetes. The genes obtained from this study showed a significant involvement in causing the disease, which may be used as a potential drug target.

Molecular dynamics of sialic acid analogues complex with cholera toxin and DFT optimization of ethylene glycol-mediated zinc nanocluster conjugation.

Cholera is an infectious disease caused by cholera toxin (CT) protein of bacterium Vibrio cholerae. A sequence of sialic acid (N-acetylneuraminic acid, NeuNAc or Neu5Ac) analogues modified in its C-5 position is modelled using molecular modelling techniques and docked against the CT followed by molecular dynamics simulations. Docking results suggest better binding affinity of NeuNAc analogue towards the binding site of CT. The NeuNAc analogues interact with the active site residues GLU:11, TYR:12, HIS:13, GLY:33, LYS:34, GLU:51, GLN:56, HIE:57, ILE:58, GLN:61, TRP:88, ASN:90 and LYS:91 through intermolecular hydrogen bonding. Analogues N-glycolyl-NeuNAc, N-Pentanoyl-NeuNAc and N-Propanoyl-NeuNAc show the least XPGscore (docking score) of -9.90, -9.16, and -8.91, respectively, and glide energy of -45.99, -42.14 and -41.66 kcal/mol, respectively. Stable nature of CT-N-glycolyl-NeuNAc, CT-N-Pentanoyl-NeuNAc and CT-N-Propanoyl-NeuNAc complexes was verified through molecular dynamics simulations, each for 40 ns using the software Desmond. All the nine NeuNAc analogues show better score for drug-like properties, so could be considered as suitable candidates for drug development for cholera infection. To improve the enhanced binding mode of NeuNAc analogues towards CT, the nine NeuNAc analogues are conjugated with Zn nanoclusters through ethylene glycol (EG) as carriers. The NeuNAc analogues conjugated with EG-Zn nanoclusters show better binding energy towards CT than the unconjugated nine NeuNAc analogues. The electronic structural optimization of EG-Zn nanoclusters was carried out for optimizing their performance as better delivery vehicles for NeuNAc analogues through density functional theory calculations. These sialic acid analogues may be considered as novel leads for the design of drug against cholera and the EG-Zn nanocluster may be a suitable carrier for sialic acid analogues.

High Level Secretion of Laccase (LccH) from a Newly Isolated White-Rot Basidiomycete, Hexagonia hirta MSF2.

Newer and novel laccases attract considerable attention due to its promising and valuable multiple applications in biotech industry. This present investigation documents, for the first time, on high level extracellular secretion of laccase (LccH) in newly isolated wood-degrading basidiomycete Hexagonia hirta MSF2. LccH was optimally active at 40°C in citrate phosphate buffer with a pH of 3.4. Optimized Cu(2+) in glucose yeast extract (GY) medium enhanced the LccH production by H. hirta to 1944.44 U.ml(-1). A further increment in LccH activity of 5671.30 U.ml(-1) was achieved by the addition of a phenolic inducer, 2,5 Xylidine. Zymogram and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis of LccH revealed that LccH is a monomer with a molecular mass of 66 kDa. MALDI-TOF-MS based peptide mass fingerprinting and comparative modeling of the amino acid sequence of LccH showed that it was closer to Trametes sp. AH28-2 (PDB: 3KW7) with 48% identity, 95% coverage, 0.011 alignment score and RMSD of 0.497Å. Crude LccH delignified lignocellulosic biomass such as wood and corncob, to a level of 28.6 and 16.5%, respectively. Such high level secretion, thermal and solvent stability of LccH make H. hirta a potential candidate not only for LccH production and biodelignification but also generation of lignin derived aromatic feed stock chemicals for industrial and environmental applications.

Algorithmic Approach for Removing the Redundancy in Diabetic Gene Categories Based on Semantic Similarity and Gene Expression Data.

Even after so much advancement in gene expression microarray technology, the main hindrance in analyzing microarray data is its limited number of samples as compared to a number of factors, which is a major impediment in revealing actual gene functionality and valuable information from the data. Analyzing gene expression data can indicate the factors which are differentially expressed in the diseased tissue. As most of these genes have no part to play in causing the disease of interest, thus, identification of disease-causing genes can reveal not just the case of the disease, but also its pathogenic mechanism. There are a lot of gene selection methods available which have the capacity to remove irrelevant genes, but most of them are not sufficient enough in removing redundancy in genes from microarray data, which increases the computational cost and decreases the classification accuracy. Combining the gene expression data with the gene ontology information can be helpful in determining the redundancy which can then be removed using the algorithm mentioned in the work. The gene list obtained after these sequential steps of the algorithm can be analyzed further to obtain the most deterministic genes responsible for type 2 diabetes.

Profiling leucocyte subsets in tuberculosis-diabetes co-morbidity.

The immune system plays an important role in the pathogenesis of pulmonary tuberculosis-type 2 diabetes mellitus (PTB-DM) co-morbidity. However, the phenotypic profile of leucocyte subsets at homeostasis in individuals with active or latent tuberculosis (LTB) with coincident diabetes is not known. To characterize the influence of diabetes on leucocyte phenotypes in PTB or LTB, we examined the frequency (Fo ) of leucocyte subsets in individuals with TB with (PTB-DM) or without (PTB) diabetes; individuals with latent TB with (LTB-DM) or without (LTB) diabetes and non-TB-infected individuals with (NTB-DM) or without (NTB) diabetes. Coincident DM is characterized by significantly lower Fo of effector memory CD4(+) T cells in LTB individuals. In contrast, DM is characterized by significantly lower Fo of effector memory CD8(+) T cells and significantly higher Fo of central memory CD8(+) T cells in PTB individuals. Coincident DM resulted in significantly higher Fo of classical memory B cells in PTB and significantly higher Fo of activated memory and atypical B cells in LTB individuals. Coincident DM resulted in significantly lower Fo of classical and intermediate monocytes in PTB, LTB and NTB individuals. Finally, DM resulted in significantly lower Fo of myeloid and plasmacytoid dendritic cells in PTB, LTB and NTB individuals. Our data reveal that coincident diabetes alters the cellular subset distribution of T cells, B cells, dendritic cells and monocytes in both individuals with active TB and those with latent TB, thus potentially impacting the pathogenesis of this co-morbid condition.

Molecular modeling of methyl-α-Neu5Ac analogues docked against cholera toxin--a molecular dynamics study.

Molecular modeling of synthetic methyl-α-Neu5Ac analogues modified in C-9 position was investigated by molecular docking and molecular dynamics (MD) simulation methods. Methyl-α-Neu5Ac analogues were docked against cholera toxin (CT) B subunit protein and MD simulations were carried out for three Methyl-α-Neu5Ac analogue-CT complexes (30, 10 and 10 ns) to estimate the binding activity of cholera toxin-Methyl-α-Neu5Ac analogues using OPLS_2005 force field. In this study, direct and water mediated hydrogen bonds play a vital role that exist between the methyl-α-9-N-benzoyl-amino-9-deoxy-Neu5Ac (BENZ)-cholera toxin active site residues. The Energy plot, RMSD and RMSF explain that the simulation was stable throughout the simulation run. Transition of phi, psi and omega angle for the complex was calculated. Molecular docking studies could be able to identify the binding mode of methyl-α-Neu5Ac analogues in the binding site of cholera toxin B subunit protein. MD simulation for Methyl-α-9-N-benzoyl-amino-9-deoxy-Neu5Ac (BENZ), Methyl-α-9-N-acetyl-9-deoxy-9-amino-Neu5Ac and Methyl-α-9-N-biphenyl-4-acetyl-deoxy-amino-Neu5Ac complex with CT B subunit protein was carried out, which explains the stable nature of interaction. These methyl-α-Neu5Ac analogues that have computationally acceptable pharmacological properties may be used as novel candidates for drug design for cholera disease.

Development and Validation of Stability-indicating High Performance Liquid Chromatographic Method for the Estimation of Everolimus in Tablets.

The present study depicts the development of a validated reversed-phase high performance liquid chromatographic method for the determination of the everolimus in presence of degradation products or pharmaceutical excipients. Stress study was performed on everolimus and it was found that it degrade sufficiently in oxidizing and acidic conditions but less degradation was found in alkaline, neutral, thermal and photolytic conditions. The separation was carried out on Hypersil BDS C18 column (100×4.6 mm, 5 µ) column having particle size 5 µ using acetate buffer:acetonitrile (50:50 v/v) with pH 6.5 adjusted with orthophosphoric acid as mobile phase at flow rate of 1 ml/min. The wavelength of the detection was 280 nm. A retention time (Rt) nearly 3.110 min was observed. The calibration curve for everolimus was linear (r(2)=0.999) from range of 25-150 µg/ml with limit of detection and limit of quantification of 0.036 µg/ml and 0.109 µg/ml, respectively. Analytical validation parameters such as selectivity, specificity, linearity, accuracy and precision were evaluated and relative standard deviation value for all the key parameters were less than 2.0%. The recovery of the drug after standard addition was found to be 100.55%. Thus, the developed RP-HPLC method was found to be suitable for the determination of everolimus in tablets containing various excipients.

Molecular simulation of N-acetylneuraminic acid analogs and molecular dynamics studies of cholera toxin-Neu5Gc complex.

Cholera toxin (CT) is an AB5 protein complex secreted by the pathogen Vibrio cholera, which is responsible for cholera infection. N-acetylneuraminic acid (NeuNAc) is a derivative of neuraminic acid with nine-carbon backbone. NeuNAc is distributed on the cell surface mainly located in the terminal components of glycoconjugates, and also plays an important role in cell-cell interaction. In our current study, molecular docking and molecular dynamic (MD) simulations were implemented to identify the potent NeuNAc analogs with high-inhibitory activity against CT protein. Thirty-four NeuNAc analogs, modified in different positions C-1/C-2/C-4/C-5/C-7/C-8/C-9, were modeled and docked against the active site of CT protein. Among the 34 NeuNAc analogs, the analog Neu5Gc shows the least extra precision glide score of -9.52 and glide energy of -44.71 kcal/mol. NeuNAc analogs block the CT active site residues HIS:13, ASN:90, LYS:91, GLN:56, GLN:61, and TRP:88 through intermolecular hydrogen bonding. The MD simulation for CT-Neu5Gc docking complex was performed using Desmond. MD simulation of CT-Neu5Gc complex reveals the stable nature of docking interaction.

Prevalence and consequences of positive blood alcohol levels among patients injured at work.

AIMS: The aim of this study was to characterize positive blood alcohol among patients injured at work, and to compare the severity of injury and outcome of blood alcohol concentration (BAC) positive and negative patients. SETTINGS AND DESIGN: A retrospective cohort study was performed at a Level 1 academic trauma center. Patients injured at work between 01/01/07 and 01/01/12 and admitted with positive (BAC+) vs negative (BAC-) blood alcohol were compared using bivariate analysis. RESULTS: Out of 823, 319 subjects were tested for BAC (38.8%), of whom 37 were BAC+ (mean 0.151 g/dL, range 0.015-0.371 g/dL). Age (41 years), sex (97.2% men), race, intensive care unit (ICU) and hospital length of stay (LOS), and mortality were similar between groups. Nearly half of BAC+ cases were farming injuries (18, 48.6%): Eight involved livestock, five involved all-terrain vehicles (ATVs), three involved heavy equipment, one fell, and one had a firearm injury. Eight (21.6%) were construction site injuries involving falls from a roof or scaffolding, five (13.5%) were semi-truck collisions, four (10.8%) involved falls from a vehicle in various settings, and two (5.4%) were crush injuries at an oilfield. BAC+ subjects were less likely to be injured in construction sites and oilfields, including vehicle-related falls (2.3 vs 33.9%, P < 0.0001). Over half of BAC+ (n = 20, 54%) subjects were alcohol dependent; three (8.1%) also tested positive for cocaine on admission. No BAC+ subjects were admitted to rehabilitation compared to 33 (11.7%) of BAC- subjects. Workers' compensation covered a significantly smaller proportion of BAC+ patients (16.2 vs 61.0%, P < 0.0001). CONCLUSIONS: Alcohol use in the workplace is more prevalent than commonly suspected, especially in farming and other less regulated industries. BAC+ is associated with less insurance coverage, which probably affects resources available for post-discharge rehabilitation and hospital reimbursement.

Molecular dynamics study of the conformations of glycosidic linkages in sialic acid modified ganglioside GM3 analogues.

The objective of the present study is to model the analogues of monosialoganglioside (GM3) by making modifications in its sialic acid residue with different substitutions in aqueous environment and to determine their structural stability based upon computational molecular dynamics. Molecular mechanics and molecular dynamics investigation was carried out to study the conformational preferences of the analogues of GM3. Dynamic simulations were carried out on the analogues of GM3 varying in the substituents at C-1, C-4, C-5, C-8 and C-9 positions of their sialic acid or Neuraminic acid (NeuAc) residue. The analogues are soaked in a periodic box of TIP3P water as solvent and subjected to a 10 ns molecular dynamics (MD) simulation using AMBER ff03 and gaff force fields with 30 ps equilibration. The analogue of GM3 with 9-N-succNeuAc (analogue5, C9 substitution) was observed to have the lowest energy of -6112.5 kcal/mol. Graphical analysis made on the MD trajectory reveals the direct and water mediated hydrogen bonds existing in these sialic acid analogues. The preferable conformations for glycosidic linkages of GM3 analogues found in different minimum energy regions in the conformational maps were identified. This study sheds light on the conformational preferences of GM3 analogues which may be essential for the design of GM3 analogues as inhibitors for different ganglioside specific pathogenic proteins such as bacterial toxins, influenza toxins and neuraminidases.

Potential anesthesia protocols for space exploration missions.

In spaceflight beyond low Earth's orbit, medical conditions requiring surgery are of a high level of concern because of their potential impact on crew health and mission success. Whereas surgical techniques have been thoroughly studied in spaceflight analogues, the research focusing on anesthesia is limited. To provide safe anesthesia during an exploration mission will be a highly challenging task. The research objective is thus to describe specific anesthesia procedures enabling treatment of pre-identified surgical conditions. Among the medical conditions considered by the NASA Human Research Program Exploration Medical Capability element, those potentially necessitating anesthesia techniques have been identified. The most appropriate procedure for each condition is thoroughly discussed. The substantial cost of training time necessary to implement regional anesthesia is pointed out. Within general anesthetics, ketamine combines the unique advantages of preservation of cardiovascular stability, the protective airway reflexes, and spontaneous ventilation. Ketamine side effects have for decades tempered enthusiasm for its use, but recent developments in mitigation means broadened its indications. The extensive experience gathered in remote environments, with minimal equipment and occasionally by insufficiently trained care providers, confirms its high degree of safety. Two ketamine-based anesthesia protocols are described with their corresponding indications. They have been designed taking into account the physiological changes occurring in microgravity and the specific constraints of exploration missions. This investigation could not only improve surgical care during long-duration spaceflights, but may find a number of terrestrial applications in isolated or austere environments.

Molecular Dynamics of Sialic Acid Analogues and their Interaction with Influenza Hemagglutinin.

Synthetic sialic acid analogues with multiple modifications at different positions(C-1/C-2/C-4/C-8/C-9) are investigated by molecular mechanics and molecular dynamics to determine their conformational preferences and structural stability to interact with their natural receptors. Sialic acids with multiple modifications are soaked in a periodic box of water as solvent. Molecular mechanics and a 2 nanosecond molecular dynamics are done using amber force fields with 30 picosecond equilibrium. Direct and water mediated hydrogen bonds existing in the sialic acid analogues, aiding for their structural stabilization are identified in this study. The accessible conformations of side chain linkages of sialic acid analogues holding multiple substituents are determined from molecular dynamics trajectory at every 1ps interval. Transitions between different minimum energy regions in conformational maps are also noticed in C-1, C-2, C-4, C-8 and C-9 substituents. Docking studies were done to find the binding mode of the sialic acid analogues with Influenza hemagglutinin. This finding provides stereo chemical explanation and conformational preference of sialic acid analogues which may be crucial for the design of sialic acid analogues as inhibitors for different sialic acid specific pathogenic proteins such as influenza toxins and neuraminidases.

Delayed treatment with plasminogen activator inhibitor-1 decoys reduces tubulointerstitial fibrosis.

We examined the capacity of delayed inhibition of plasminogen activator inhibitor-1 (PAI-1) to reduce tubulointerstitial fibrosis induced by unilateral ureteral obstruction (UUO) in mice. Small peptides mimicking parts of urokinase (uPA) and tissular plasminogen activator (tPA) and serving as decoy molecules for PAI-1 were administered daily during the late stages (3 to 8 days) of UUO. Treatment with PAI-1 decoys reduced interstitial deposition of fibronectin, collagen III and collagen IV without changes in macrophage and myofibroblast infiltration. Interestingly, while PAI-1 activity was reduced and the combined uPA and tPA activity was increased, the antifibrotic effect was obtained without modification of plasmin activity but with increased of hepatocyte growth factor (HGF) expression. We show for the first time that treatment with small PAI-1 decoy peptides reduces established tubulointerstitial fibrosis. This protective effect probably resulted from increased degradation of the extracellular matrix by an HGF dependent mechanism.

Detection and molecular characterization of Giardia isolated from recreational lake water in Malaysia.

Nine 50-l surface water samples from a Malaysian recreational lake were examined microscopically using an immunomagnetisable separation-immunofluorescent method. No Cryptosporidium oocysts were detected, but 77.8% of samples contained low numbers of Giardia cysts (range, 0.17-1.1 cysts/l), which were genetically characterised by SSU rRNA gene sequencing. Genotype analyses indicated the presence of Giardia duodenalis assemblage A suggesting potential risk to public health. The present study represents the first contribution to our knowledge of G. duodenalis assemblages in Malaysian recreational water.

Conformations of higher gangliosides and their binding with cholera toxin - investigation by molecular modeling, molecular mechanics, and molecular dynamics.

Molecular mechanics and molecular dynamics studies are performed to investigate the conformational preference of cell surface higher gangliosides (GT1A and GT1B) and their interaction with Cholera Toxin. The water mediated hydrogen bonding network exists between sugar residues in gangliosides. An integrated molecular modeling, molecular mechanics, and molecular dynamics calculation of cholera toxin complexed with GT1A and GT1B reveal that, the active site of cholera toxin can accommodate these higher gangliosides. Direct and water mediated hydrogen bonding interactions stabilize these binding modes and play an essential role in defining the order of specificity for different higher ganglioside towards cholera toxin. This study identifies that the binding site of cholera toxin is shallow and can accommodate a maximum of two NeuNAc residues. The NeuNAc binding site of cholera toxin may be crucial for the design of inhibitors that can prevent the infection of cholera.