May disordered protein cause serious drug side effect?

Beware of docking!

“…In our experience, translating drug discovery from CADD to clinical trials is difficult. For example, some top potent hits screened by docking from the TCM database failed in the final bioactivity test [20,[22][23][24][25][26][27]. However, if a hit comes first from a bioassay -for example, if it was screened from high-throughput screening (HTS) by 'automation-friendly' robotics, data processing, and control software in vitro -then it is easier to move to in vivo.…”

“…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.…”

“…[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.…”

Insight into HIV of IFN-Induced Myxovirus Resistance 2 (MX2) Expressed by Traditional Chinese Medicine

“…While the docking site consists of a disorder region, the drug docks to protein hardly and the complex will stabilize with difficultly. The cited references [17, 37] denote that the ligand docks into the disorder region may have weaker side effect than the widespread domain. Therefore, the disorder region should be defined as a hard work for drug design and not a bad docking site for selection.…”

“…As a result of the prediction, we can decide the character of the docking site and the efficacy of the drug [17, 37]. …”