In silico drug target identification, which includes many distinct algorithms for finding disease genes and proteins, is the first step in the drug discovery pipeline. When the 3D structures of the targets are available, the problem of target identification is usually converted to finding the best interaction mode between the potential target candidates and small molecule probes. Pharmacophore, which is the spatial arrangement of features essential for a molecule to interact with a specific target receptor, is an alternative method for achieving this goal apart from molecular docking method. PharmMapper server is a freely accessed web server designed to identify potential target candidates for the given small molecules (drugs, natural products or other newly discovered compounds with unidentified binding targets) using pharmacophore mapping approach. PharmMapper hosts a large, in-house repertoire of pharmacophore database (namely PharmTargetDB) annotated from all the targets information in TargetBank, BindingDB, DrugBank and potential drug target database, including over 7000 receptor-based pharmacophore models (covering over 1500 drug targets information). PharmMapper automatically finds the best mapping poses of the query molecule against all the pharmacophore models in PharmTargetDB and lists the top N best-fitted hits with appropriate target annotations, as well as respective molecule’s aligned poses are presented. Benefited from the highly efficient and robust triangle hashing mapping method, PharmMapper bears high throughput ability and only costs 1 h averagely to screen the whole PharmTargetDB. The protocol was successful in finding the proper targets among the top 300 pharmacophore candidates in the retrospective benchmarking test of tamoxifen. PharmMapper is available at http://59.78.96.61/pharmmapper.

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In this study, a combined simulation and experimental approach is utilized to investigate the influence of hatch spacing on the microstructure and as-built quality of 316L stainless steel (SS) samples fabricated by selective laser melting (SLM). A three-dimensional finite element model (FEM) is employed to investigate heat transfer and melt pool during the SLM of 316L SS. The phase transformation and variation of the thermo-physical properties of the materials are considered in this model. The effects of hatch spacing (H) on the temperature field, microstructure and melt pool size, overlap rate, surface quality, and relative density during the SLM of 316L SS are investigated. The simulated results indicate that, as the hatch spacing increases, the depth increases and the width of the melt pool decreases. Meanwhile, with the increase of hatch spacing, the simulated temperature of the subsequent tracks falls below the melting temperature of the first track. Moreover, the microstructures were found to coarsen with the increasing hatch spacing due to the reduced cooling rate. The optimized hatch spacing and overlap rate between adjacent tracks were obtained from numerical simulations. Simulation results illustrate that, when the optimized hatch spacing of 100 μm is adopted, fully dense parts with a smooth surface can be fabricated by SLM, thus experimentally validating the simulation results.

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