Fragment-Based Drug Discovery (FBDD) has been recognized as a newly emerging lead discovery methodology that involves biophysical fragment screening and chemistry-driven fragment-to-lead stages. Although fragments, dened as structurally simple and small compounds (typically <300 Da), have not been employed in conventional highthroughput screening (HTS), the recent signiˆcant progress in the biophysical screening methods enables fragment screening at a practical level. The intention of FBDD primarily turns our attention to weakly but speciˆcally binding fragments (hit fragments) as the starting point of medicinal chemistry. Hit fragments are then promoted to more potent lead compounds through linking or merging with another hit fragment and/or attaching functional groups. Another positive aspect of FBDD is ligand e‹ciency. Ligand e‹ciency is a useful guide in screening hit selection and hit-to-lead phases to achieve lead-likeness. Owing to these features, a number of successful applications of FBDD to``undruggable targets'' (where HTS and other lead identiˆcation methods failed to identify useful lead compounds) have been reported. As a result, FBDD is now expected to complement more conventional methodologies. This review, as an introduction of the following articles, will summarize the fundamental concepts of FBDD and will discuss its advantages over other conventional drug discovery approaches.
The impingement of a single droplet on a liquid film is observed using a high-speed video camera. Specifically, an experiment is conducted to simulate the impingement behaviors of a fuel droplet on an engine oil film in a real engine. The droplets are composed of n-heptane and ethanol. The films pertain to engine oils with two viscosities. The impact of the engine oil type, droplet liquid type, droplet release height, and temperature and thickness of the oil film on the collision phenomenon is evaluated. The design of experiments scheme is used to identify the dominant parameters affecting the crown height and splash generation. The dominant parameters for the crown height are the oil film temperature, which affects the oil viscosity; droplet release height, which is related with the impinging velocity, and oil film thickness. The splash phenomena can be divided into two types, specifically, splash phenomena with split early type and crown break type, which are affected by the droplet release height and oil film temperature, respectively. The results demonstrate that the design of experiments scheme can help evaluate the dominant parameters in impingement phenomena.
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