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The binding of a small molecule ligand to its protein target is most often characterized by binding affinity and is typically viewed as an on/off switch. The more complex reality is that binding involves the ligand passing through a series of intermediate states between the solution phase and the fully bound pose. We have performed a set of 29 unbiased molecular dynamics simulations to model the binding pathways of the dopamine receptor antagonists clozapine and haloperidol binding to the D2 and D3 dopamine receptors. Through these simulations we have captured the binding pathways of clozapine and haloperidol from the extracellular vestibule to the orthosteric binding site and thereby, we also predict the bound pose of each ligand. These are the first long time scale simulations of haloperidol or clozapine binding to dopamine receptors. From these simulations, we have identified several important stages in the binding pathway, including the involvement of Tyr7.35 in a "handover" mechanism that transfers the ligand between the extracellular vestibule and Asp3.32. We have also performed interaction and cluster analyses to determine differences in binding pathways between the D2 and D3 receptors and identified metastable states that may be of use in drug design.

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In this paper, the correlation between the electrochromic performance and the surface morphology of the tungsten trioxide (WO 3 ) thin films sputtered by dc reactive magnetron sputtering with widely varying target-substrate distances was investigated. It is found that the optical density change (∆OD) of films is strongly affected by the target-substrate distance. The coloration efficiency (CE) at 633 nm was also found to be sensitive to the target-substrate distance, with 16 cm 2 /C of film sputtered at 6 cm and 50 cm 2 /C at 18 cm. X-ray diffraction showed that the crystal structure of films was amorphous. By using atomic force microscope to identify the surface porosity of the sputtered WO 3 films, we found that the film at longer target-substrate distance was rough, porous, and having a cone-shaped columns morphology, thus offering a good electrochromic performance for opto-switching applications.

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A prototype contact-type micro piezoresistive shear-stress sensor that can be utilized to measure the shear stress between skin of stump and socket of above-knee (AK) prosthesis was designed, fabricated and tested. Micro-electro-mechanical system (MEMS) technology has been chosen for the design because of the low cost, small size and adaptability to this application. In this paper, the finite element method (FEM) package ANSYS has been employed for the stress analysis of the micro shear-stress sensors. The sensors contain two transducers that will transform the stresses into an output voltage. In the developed sensor, a 3000 3000 300 m 3 square membrane is formed by bulk micromaching of an n-type 100 monolithic silicon. The piezoresistive strain gauges were implanted with boron ions with a dose of 10 15 atoms/cm 2 . Static characteristics of the shear sensor were determined through a series of calibration tests. The fabricated sensor exhibits a sensitivity of 0.13 mV/mA-MPa for a 1.4 N full scales shear force range and the overall mean hysteresis error is than 3.5%. In addition, the results simulated by FEM are validated by comparison with experimental investigations. [607]Index Terms-Finite element method, micro-electro-mechanical system, piezoresistive, shear-stress sensor, transducer.