ISDN2012_0188: Multiphoton ultraviolet microscopy images dopamine dynamics in live brain tissue

The selection of NEs based on sensitivity analysis, employing Artificial Neural Network (ANN) using NeuroSolutions V5, was conceded. Ligand selection was then followed by a detailed interaction studies using a more focused fragment-based geometrical optimization (isobolographic analysis) which was further later substantiated through the use of docking studies (Glide 4.0) and design of experiments. Results and discussion: Curcumin and glycosylated nornicotine demonstrated higher sensitivities toward energy minimizations with A P based upon the Mean Square Error and input–output mapping via ANN (Fig. 2). Interestingly, curcumin formed Hbonds with the alanine residues and were capable of binding to the aliphatic amino acids residues (A 12–28; Glide score: −3.79) whereas the glucose side-chain of glycosylated nornicotine exhibited H-bonding with histidine and phenylalanine (AMBER) and with glutamine, phenylalanine and aspartic acid during the docking studies (Glide score: −2.89; Fig. 3). A highly synergistic interaction was observed, using an isobolographic analysis and Loewe additivity relationship (Quantitative parameter ( ): 0.45),displaying a possible reduction in individual effective concentration by a factor of 4 and 5, respectively, without compromising and even substantiating the therapeutic benefit. A neuroprotective combination of three molecules of Curcumin and three molecules of Glyconornicotine was proposed by the DoE model indicating a possible 1:1 combination with maximum of three molecules of each NE per A P oligomer. Conclusion: Our work offers a novel mathematical and in silico approach that constitutes a new frontier in providing neuroscientists with a template for in vitro and in vivo molecular experimentation.