BackgroundN-Acetylserotonin O-methyltransferase (ASMT) is an enzyme which by converting nor-melatonin to melatonin catalyzes the final reaction in melatonin biosynthesis in tryptophan metabolism pathway. High Expression of ASMT gene is evident in PPTs. The presence of abnormally high levels of ASMT in pineal gland could serve as an indication of the existence of pineal parenchymal tumors (PPTs) in the brain (J Neuropathol Exp Neurol 65: 675–684, 2006). Different levels of melatonin are used as a trait marker for prescribing the mood disorders e.g. Seasonal affective disorder, bipolar disorder, or major depressive disorder. In addition, melatonin levels can also be used to calculate the severity of a patient’s illness at a given point in time.MethodsSeventy three melatoninergic inhibitors were docked with acetylserotonin-O-methyltransferase in order to identify the potent inhibitor against the enzyme. The chemical nature of the protein and ligands greatly influence the performance of docking routines. Keeping this fact in view, critical evaluation of the performance of four different commonly used docking routines: AutoDock/Vina, GOLD, FlexX and FRED were performed. An evaluation criterion was based on the binding affinities/docking scores and experimental bioactivities.Results and conclusionResults indicated that both hydrogen bonding and hydrophobic interactions contributed significantly for its ligand binding and the compound selected as potent inhibitor is having minimum binding affinity, maximum GoldScore and minimum FlexX energy. The correlation value of r2 = 0. 66 may be useful in the selection of correct docked complexes based on the energy without having prior knowledge of the active site. This may lead to further understanding of structures, their reliability and Biomolecular activity especially in connection with bipolar disorders.

Shigella sonnei is one of the major causes of shigellosis in technically advanced countries and reports of its unprecedented increase are published from the Middle East, Latin America, and Asia. The pathogen exhibits resistance against first and second line antibiotics which highlights the need for the development of an effective broad-spectrum vaccine. A computational based approach comprising subtractive reverse vaccinology was used for the identification of potential peptide-based vaccine candidates in the proteome of S. sonnei reference strain (53G). The protocol revealed three essential, host non-homologous, highly virulent, antigenic, conserved and adhesive vaccine proteins: TolC, PhoE, and outer membrane porin protein. The cellular interactome of these proteins supports their direct and indirect involvement in biologically significant pathways, essential for pathogen survival. Epitope mapping of these candidates reveals the presence of surface exposed 9-mer B-cell-derived T-cell epitopes of an antigenic, virulent, non-allergen nature and have broad-spectrum potency. In addition, molecular docking studies demonstrated the deep binding of the epitopes in the binding groove and the stability of the complex with the most common binding allele in the human population, DRB1*0101. Future characterization of the screened epitopes in order to further investigate the immune protection efficacy in animal models is highly desirable.

A quantum mechanical charge field (QMCF) molecular dynamics (MD) simulation including the first and second hydration shells in the QM region has been carried out to describe the structural and dynamical properties of Be(2+) in aqueous solution. In this methodology, the full first and second hydration shells are treated by ab initio quantum mechanics supplemented by a fluctuating electrostatic embedding technique. From the simulation, structural properties were extracted and were found to be in good agreement with previously published experimental and theoretical results. The radial distribution function (RDF) showed the maximum probability of the Be-O bond length at 1.62 A. The first tetrahedrally arranged hydration shell is highly inert with respect to ligand-exchange processes. Application of local-density-corrected three-body correlation analysis showed minor structural influence of the ion beyond the second hydration layer, contrary to the findings of a previous QM/MM MD simulation. The dynamics of the hydrate were studied in terms of ligand mean residence times (MRTs) and the power spectrum of the Be(2+)-O stretching frequency. A comparison of the "classical" QM/MM framework with the QMCF method clearly demonstrated the advantages of the latter, as ambiguities arising from the coupling of the subregions occurring in QM/MM MD simulations did not appear when the QMCF ansatz was applied.

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Quantum mechanical/molecular mechanical (QM/MM) and quantum mechanical charge field (QMCF) molecular (MD) simulations have been performed to describe structural and dynamical properties of Na(I) and K(I) in water and to compare the two approaches. The first and second hydration shells were treated by ab initio quantum mechanics at the restricted Hartree-Fock (RHF) level. The structural data are in good agreement with previously published experimental and theoretical results. A considerable number of water exchange reactions were observed within the first shell during the simulation time of 12 ps. The number of exchange events in both shells is higher in the case of K(I) than Na(I) reflecting the weaker ion-ligand bond strength of K(I). Comparison of the "conventional" QM/MM framework with the QMCF method clearly indicates the latter to be advantageous, as ambiguities arising from the coupling of the subregions occurring in the QM/MM MD simulations did not evolve when the QMCF ansatz was applied.