01490nas 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-001921nas a2200193 4500008004100000022001400041245014800055210006900203260007100272300001600343490000800359520112400367100001901491700001901510700001801529700002501547700002601572856012901598 2014 eng d a1520-610600aMicroscopic hydration properties of the a beta(1-42) peptide monomer and the globular protein ubiquitin: a comparative molecular dynamics study0 aMicroscopic hydration properties of the a beta142 peptide monome a1155 16TH ST, NW, WASHINGTON, DC 20036 USAbAMER CHEMICAL SOCcOCT a11591-116040 v1183 a

Atomistic molecular dynamics simulations of eight selected conformations of a disordered protein amyloid beta (1-42) (A beta), and a globular protein, ubiquitin(UBQ), have been carried out in aqueous media at 310 K. Detailed analyses were carried out to compare the microscopic properties of water molecules present in the hydration layers of these systems. It is notices that irrespective of the conformational heterogeneity among the A beta monomers, water molecules hydrating UBQ. Importantly, the conformational heterogeneity of the A beta monomers has been found to affect the translational and rotational motions of hydration water molecules in a nonuniform manner. Detailed investigation of the timescale of hydrogen bond relaxations at the surface and their energetics revealed the possibility of heterogeneous confinement around different A beta conformations. The distribution of water density fluctuation around A beta conformations are broader compared density fluctuation among the A beta monomers suggests that the structural propensities could affect the peptides effective surface hydrophobicity.

1 aJose, Jaya, C.1 aKhatua, Prabir1 aBansal, Nupur1 aSengupta, Neelanjana1 aBandyopadhyay, Sanjoy uhttp://library.ncl.res.in/content/microscopic-hydration-properties-beta1-42-peptide-monomer-and-globular-protein-ubiquitin-002256nas a2200217 4500008004100000022001400041245010300055210006900158260009100227300001200318490000600330520141100336100002301747700001901770700002501789700002501814700002201839700002501861700002501886856012701911 2014 eng d a1932-620300aMolecular investigations of protriptyline as a multi-target directed ligand in alzheimer's disease0 aMolecular investigations of protriptyline as a multitarget direc a1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USAbPUBLIC LIBRARY SCIENCEcAUG ae1051960 v93 a

Alzheimer's disease (AD) is a complex neurodegenerative disorder involving multiple cellular and molecular processes. The discovery of drug molecules capable of targeting multiple factors involved in AD pathogenesis would greatly facilitate in improving therapeutic strategies. The repositioning of existing non-toxic drugs could dramatically reduce the time and costs involved in developmental and clinical trial stages. In this study, preliminary screening of 140 FDA approved nervous system drugs by docking suggested the viability of the tricyclic group of antidepressants against three major AD targets, viz. Acetylcholinesterase (AChE), beta-secretase (BACE-1), and amyloid beta (A beta) aggregation, with one member, protriptyline, showing highest inhibitory activity. Detailed biophysical assays, together with isothermal calorimetry, fluorescence quenching experiments, kinetic studies and atomic force microscopy established the strong inhibitory activity of protriptyline against all three major targets. The molecular basis of inhibition was supported with comprehensive molecular dynamics simulations. Further, the drug inhibited glycation induced amyloid aggregation, another important causal factor in AD progression. This study has led to the discovery of protriptyline as a potent multi target directed ligand and established its viability as a promising candidate for AD treatment.

1 aBansode, Sneha, B.1 aJana, Asis, K.1 aBatkulwar, Kedar, B.1 aWarkad, Shrikant, D.1 aJoshi, Rakesh, S.1 aSengupta, Neelanjana1 aKulkarni, Mahesh, J. uhttp://library.ncl.res.in/content/molecular-investigations-protriptyline-multi-target-directed-ligand-alzheimers-disease-0