This low hit rate has limited the usage of HTS to research programs capable of screening large compound libraries. However, although traditional HTS often results in multiple hit compounds, some of which are capable of being modified into a lead and later a novel therapeutic, the hit rate for HTS is often extremely low. The method has the advantage of requiring minimal compound design or prior knowledge, and technologies required to screen large libraries have become more efficient. This brute force approach relies on automation to screen high numbers of molecules in search of those that elicit the desired biologic response. Although progress was being made in CADD, the potential for high-throughput screening (HTS) had begun to take precedence as a means for finding novel therapeutics. Some have credited this as being the start of intense interest in the potential for computer-aided drug design (CADD). On October 5, 1981, Fortune magazine published a cover article entitled the “Next Industrial Revolution: Designing Drugs by Computer at Merck” ( Van Drie, 2007). Finally, computational methods for toxicity prediction and optimization for favorable physiologic properties are discussed with successful examples from literature. In addition, important tools such as target/ligand data bases, homology modeling, ligand fingerprint methods, etc., necessary for successful implementation of various computer-aided drug discovery/design methods in a drug discovery campaign are discussed. We review widely used ligand-based methods such as ligand-based pharmacophores, molecular descriptors, and quantitative structure-activity relationships. Ligand-based methods use only ligand information for predicting activity depending on its similarity/dissimilarity to previously known active ligands. The article discusses theory behind the most important methods and recent successful applications. Structure-based approaches include ligand docking, pharmacophore, and ligand design methods. Structure-based methods are in principle analogous to high-throughput screening in that both target and ligand structure information is imperative. These methods are broadly classified as either structure-based or ligand-based methods. Due to the superiority of the Mn 4+-doped fluoride for the rapid imaging of LFPs in terms of low-cost, high compatibility and good availability, it is expected to be a promising candidate for forensic science as well as fluorescence imaging in other fields instead of rare earth luminescent materials.Computer-aided drug discovery/design methods have played a major role in the development of therapeutically important small molecules for over three decades. To confirm the high selectivity of KAF:Mn 4+-OA for LFP imaging, an efficient quantitative evaluation method is proposed with the aid of ImageJ & Origin software. The well-defined ridge details with little background interference on various surfaces were presented by the oleic acid (OA) modified KAF:Mn 4+ (KAF:Mn 4+-OA) phosphor in few seconds using the powder dusting method. More importantly, this non-ultraviolet (UV) or non-near infrared (NIR) induced phosphor was proved to be an ideal fluorescent label for LFP imaging, which is both friendly for touch DNA analysis and compatible to forensic light sources. The phosphor has a uniform and superfine morphology with excellent luminescence properties. To overcome this challenge, a moisture-stable, red-emitting fluoride phosphor K 3AlF 6:Mn 4+ (KAF:Mn 4+) with an organic hydrophobic skin was prepared. The demand for in-situ detection of latent fingerprints (LFPs) in ways of high sensitivity, high selectivity, high contrast, low cost and user-friendly is still urgent.
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