**4.1 Computational methods**

Although high through put screening (HTS) and many assay techniques available, it is difficult to predict drug and target interaction and its subsequence consequences [31]. Every drug bind with variety of targets but most of them attach with proteins that present in the form of receptors, ion channels, enzymes, antigen and transcriptional factors [32]. To screen the drugs interaction with every of this target is not possible and also it consumes lots of time and money. Certain computational approaches are available that able to screen thousands of test drug molecule with many targets within short time period. The selection of drug and its possible targets are based on similarities based on structure, its protein binding and typical side effects that drugs produce [33–35]. Many molecular docking software are available that predict binding of drug molecule within active site of the target and able to predict the three-dimensional interaction at atomic level. In this approach it is necessary to discover protein structures of both normal and disease condition to target it in proper way else binding of drug with normal protein structure may lead to side effects. Computational approach needs lots of information that can be derived from various databases and webservers like DrugBank [36], E medstore [37], KEGG: Kyoto Encyclopedia of Genes and Genomes [38], SuperTarget and Manually Annotated Targets and Drugs Online Resource (MATADOR) [39], Potential Drug Target Database (PDTD) [40], ZINC [41], CancerDR [42] and many others. Computational models broadly categorized in to network based model that working based on the principles of multiple target optimal intervention (MTOI) [43], Drug side-effect similarity-based method [35] and machine learning-based model that further categorized into supervised learning method and semi-supervised learning method [32].

## **4.2 Biological experimental approaches**

In this method the interaction in between drug and its target is determined. To accomplish this, we may fix the drugs on certain bead and allowing reaction of washing cell lysate extracts with drugs [44]. It is also possible to carry out highthroughput screening based direct-binding assays to test drugs against certain kinases [45]. Cell based screening examine the evidence of autophagy, apoptosis or inhibition of proliferation in proper cell culture environment of different cancer cells [46–48]. Also, genetic expression study of drugs based on cell line can help in drug repurposing.
