A new approach used in docking study for predicting the combination drug efficacy in EML4-ALK target of NSCLC

Abstract

Combination drug treatments are usually used in many diseases, including cancers and AIDS. This treatment strategy is known as one of the cornerstone in therapies, which potentially reduces drug toxicity and drug resistance and also enhances therapeutic efficacy. Before using a drug in treatment, several experimental studies are done in vivo and in vitro to ensure the drug’s efficacy. In such experimental studies, the drug’s efficacy is evaluated with the help of drug dose ratio. In the combination drug experimental studies, the efficacy of the drugs is quantified with the Combination Index (CI) value and then interpreted by various terminologies like synergy, additive, and antagonism. Several computational models have now been invented for the speedy identification of combination drug efficacy. Unfortunately, none of these models have predicted the atomic level interaction of the combination drug with the target protein. This type of intermolecular interaction can be identified with the help of docking software. In the proposed work, we try to identify the intermolecular interaction and efficacy of the combination drug Crzizotinib and Temozolomide in the target of EML4-ALK in NSCLC by in silico study. The result of the study was evaluated with drug properties and Complex Energy (CE) of the docked complex rather than using docking score and binding energy. From this study, we could understand that first, Crizotinib and then after the Temozolomide drug binded on the EML4-ALK protein complex, showed very least CE and also identified that the combination of Crizotinib and Temozolomide drug are more effective in NSCLC.

Communicated by Ramaswamy H. Sarma

Keywords:

• Combination drug
• synergism
• RTKs
• NSCLC
• cancer

Acknowledgments

We would like to thanks the University of Kerala, the State Interuniversity Center of Excellence in Bioinformatics (SIUCE, Govt. of Kerala), Dept. of Biotechnology (DBT-BIF project), Govt. of India. for providing all the facilities for doing this work.

Availability of data and material

All necessary data generated or analyzed during this study are included in this article. Any additional data could be available from the corresponding author upon request.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Author’s contributions

SY performed all the research activities, VC and ASN monitored the research work and SY, JI and VC participated in preparing and drafting the manuscript. All authors read and approved the final manuscript.