iSMART: An Integrated Cloud Computing Web Server for Traditional Chinese Medicine for Online Virtual Screening,de novoEvolution and Drug Design

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.…”

“…[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]. In our experience, translating drug discovery from CADD to clinical trials is difficult.…”

“…From Figure 4, it seems that only the induced-fit mode will change the shape of the binding pocket. However, the entry into the binding pocket will sometimes change the shape of the binding site, according to simulation from MD experiments [16,19,20,23,31]. When type of shift occurs with ligand binding, rigid docking programs will not provide useful answers.…”

“…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.…”

Denovo Designing, Virtual Screening and Lead Optimization of Potential Drug Candidate for Herpes Disease

“…In these web servers many techniques were combined (pharmacophore mapping, similarity calculation, scoring, and target identification) to create a web interface which was more consistent and user friendly. Hartenfeller and Schneider have also emphasized that novel biologically active drug like lead molecules can be generated computationally on the basis of rule based fragment assembly [24]. Our initial hit molcule was also generated by fragment assembly method of e-LEA3D.…”