iScreen: world’s first cloud-computing web server for virtual screening and de novo drug design based on TCM database@Taiwan

Abstract

The rapidly advancing researches on traditional Chinese medicine (TCM) have greatly intrigued pharmaceutical industries worldwide. To take initiative in the next generation of drug development, we constructed a cloud-computing system for TCM intelligent screening system (iScreen) based on TCM Database@Taiwan. iScreen is compacted web server for TCM docking and followed by customized de novo drug design. We further implemented a protein preparation tool that both extract protein of interest from a raw input file and estimate the size of ligand bind site. In addition, iScreen is designed in user-friendly graphic interface for users who have less experience with the command line systems. For customized docking, multiple docking services, including standard, in-water, pH environment, and flexible docking modes are implemented. Users can download first 200 TCM compounds of best docking results. For TCM de novo drug design, iScreen provides multiple molecular descriptors for a user's interest. iScreen is the world's first web server that employs world's largest TCM database for virtual screening and de novo drug design. We believe our web server can lead TCM research to a new era of drug development. The TCM docking and screening server is available at http://iScreen.cmu.edu.tw/.

Beware of docking!

“…There are several docking programs for a user to choose from based on his or her particular requirements. At present, docking algorithms emphasize different aspects of structure-based drug design (SBDD), such as fragment-based drug design [11][12][13], flexible docking [14], docking in water, solvation, and specific pH [15,16]. For example, if we need to screen more than 10 000 compounds from a database, then flexible docking maybe not a good choice unless we have a very powerful and high-speed computer.…”

“…Provided by the Skolnick Research Group. [170] Opinion environment, and flexible docking can be performed [15]. The iSMART services, including the TCM drug network, TCM-pathway-disease network, and ligand-based drug design, were brought online to seal the gaps between TCM studies and computational systems biology and network analysis [16], and some new algorithms were developed for drug design and screening [18][19][20][21].…”

“…Basically, if one can do the regression of bioactivity versus scoring function, then we can choose the best regression of scoring function as the evaluation criteria. To try to improve accuracy of screening and determine viable compounds for clinical trials, we have developed a website which integrates TCM and a computational systems biology tool (iSMART) [16]; including the docking webserver iScreen [15] to screen the TCM database [17]. The user can upload their protein structure downloaded from the PDB, and the webserver contains some useful modes such as customized docking, standard, aqueous, pH environment, and flexible docking.…”

Identification of new potent inhibitors of dengue virus NS3 protease from traditional Chinese medicine database

“…The serine protease N-terminal domain of NS3 was selected for virtual screening of small molecules from TCM database. Prepare Protein tool of iScreen server [38] was used for preparing the protein for virtual screening (http://iscreen.cmu.edu.tw/ligand.php). All the visualizations of molecular structure were performed with Pymol [9] and Ligplot [15,41] which are very powerful software, for all purpose molecular visualizations.…”

Design of Glucagon‐Like Peptide‐1 Receptor Agonist for Diabetes Mellitus from Traditional Chinese Medicine

“…Thus it is possible that we can design appropriate drugs to be GLP-1 receptor agonist. Computer-aided drug design (CADD) is a time-saving method to filter large amounts of small compounds by computational simulation [55]. CADD has been widely used in the forward-looking treatment of diseases [56, 57].…”