Editorial [Hot Topic: High Throughput Technologies in Drug Discovery (Guest Editor: Bijoy Kundu)]

In today's interdisciplinary aspects of drug discovery, researchers frequently need to keep in touch with events in fields different from their own. Among various approaches being applied, the recent trend is to increase the speed and efficiency of drug discovery, from hit identification all the way through to the creation of therapeutic candidates. This has led to huge investments by major pharmaceutical companies/academia's in a variety of high-throughput technologies, with emphasis on synthesizing more compounds, identifying targets, screening them faster and delivery systems; all at reduced cost per compound. These high-throughput technologies have the greatest potential to affect drug discovery as part of the ‘closed-loop’ process, in which numerous compounds are selected for synthesis from a ‘virtual library’ of compounds that could be made by parallel chemistry methods. The process is repeated, and improved active compounds are followed up again, using highthroughput computational methods to aid compound selection, in further loops until the desired compound properties have been achieved. The present issue of Combinatorial & High Throughput Screening brings reviews focused on recent application of highthroughput technologies to identify new drugs. Modern drug discovery technologies in lead discovery have been reviewed with special emphasis on the key components underlying the integration between experimental and computational methods in drug design, highlighting progresses, challenges and future directions. There is also a review devoted to state-of-art methodologies dedicated to virtual highthroughput screenings in new lead identification. The lead optimization and new lead design have been illustrated with examples with emphasis on a combination of general and target specific screening protocols. These advanced experimental methods used for HTS at various steps of drug discovery over the years have generated data of the order terabytes. The need to manage this enormous data has led computing scientists to offer Cloud computing tool which has been reviewed with focus on speed, efficiency and cost effectiveness to accelerate drug discovery. One key point in the development of virtual screening is the accuracy of docking simulation and the accuracy may vary depending on what target is being tested and what kind of molecules composes the screening library. Besides, to accelerate the process of design of new drugs with specific desirable physicochemical and/or biological activity profiles, machine learning, computational pattern recognition or statistical modelling algorithms are needed to generate quantitative correlations between molecular structures and chemical properties or biological activities. Such modelling can be undertaken either with the knowledge of the structure of the biological target (Structure-based screening) involved in the activity or even in the absence of any knowledge of the target structure (Ligand-based screening). A comprehensive review based on both the screening techniques describing methodology, applications and limitations has been discussed. This is followed by a review, summarizing a combination approach using ligand based screening (SVM) and receptor based screening (molecular docking) to facilitate the rapid screening of proteasome inhibitors from large compound library. The method appears to be swift and precise enough leading to the identification of novel and potential proteasome inhibitors of β subunit of P. falciparum and can be a good starting point for developing novel antimalarial drugs. As part of a close loop process in drug discovery, the various approaches to foster the integration of virtual screening with target-based HTS have been reviewed by providing several success stories that will benefit the early-stage drug discovery. Besides, synthesis and screening of compounds in highthroughput mode, combinatorial approach have also been used for safe delivery systems. Recent developments in combinatorial syntheses and parallel screening of cationic polymer libraries for the discovery of efficient and safe gene delivery will be reviewed in this issue.