Three-dimensional pharmacophore screening for fentanyl derivatives

Fentanyl is a highly selective u-opioid receptor agonist with high analgesic activity. Three-dimensional pharmacophore models were built from a set of 50 fentanyl derivatives. These were employed to elucidate ligand-receptor interactions using information derived only from the ligand structure to identify new potential lead compounds. The present studies demonstrated that three hydrophobic regions, one positive ionizable region and two hydrogen bond acceptor region sites located on the molecule seem to be essential for analgesic activity. The results of the comparative molecular field analysis model suggested that both steric and electrostatic interactions play important roles. The contributions from steric and electrostatic fields for the model were 0.621 and 0.379, respectively. The pharmacophore model provides crucial information about how well the common features of a subject molecule overlap with the hypothesis model, which is very valuable for designing and optimizing new active structures.

Pharmacophore Screening on Piperidinecarboxamides Derivatives Based on GALAHAD and CoMFA Models

In order to discover the novel anticonvulsant drugs, pharmacophore screening of the anticonvulsant inhibitors was enforced. Genetic Algorithm with Linear Assignment for Hypermolecular Alignment of Datasets （GALAHAD） and Comparative Molecular Field Analysis （CoMFA） studies were combined to implement our research. Firstly, multiple models were generated using GALAHAG based on high active molecules. Secondly, several of them were validated using the CoMFA study. Finally, a good values of q2 from training set and promising predictive power from test set were obtained based on one model simutaneously. One model had been selected as the most reasonable pharmacophore model. The results of the CoMFA study based on the model 1 suggested that both steric and electrostatic interactions played important roles.

Blind false data injection attacks in smart grids subject to measurement outliers

False data injection attacks(FDIAs)can manipulate measurement data from Supervisory Control and Data Acquisition(SCADA)system and threat state estimation in smart grids.Blind FDIAs(BFDIAs)enhance traditional FDIAs,which eliminate the limitation of grasping measurement Jacobian matrix H in advance,but when there are outliers in measurement data,attack performance is degraded.In this paper,improved BFDIAs are proposed.In off-line phase,lowdimensional measurement matrix without outliers calculated by Linear Local Tangent Space Alignment algorithm(LLTSA)is sent into Continuous Deep Belief Network(CDBN)as training data to learn their probability distribution.In on-line phase,real-time low-dimensional measurement matrix with outliers are sent into the trained model as inputs,and outputs are reconstructed by the probability distribution in off-line phase,which eliminates the influence of outliers indirectly.Simulations are implemented on PJM 5-bus and IEEE 14-bus systems to verify the performance of proposed strategy compared with PCA-based BFDIAs.