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Correction to: Exploration for novel inhibitors showing back-to-front approach against VEGFR-2 kinase domain (4AG8) employing molecular docking mechanism and molecular dynamics simulations.

ABSTRACT: Following publication of the original article [1], the authors reported errors in Figure 3, Figure 14a, Figure 18, Figure 19b, Additional file 3 and Additional file 7.

SUBMITTER: Rampogu S

PROVIDER: S-EPMC6933660 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Correction to: Exploration for novel inhibitors showing back-to-front approach against VEGFR-2 kinase domain (4AG8) employing molecular docking mechanism and molecular dynamics simulations.

Rampogu Shailima S Baek Ayoung A Zeb Amir A Lee Keun Woo KW

BMC cancer 20191226 1

Following publication of the original article [1], the authors reported errors in Figure 3, Figure 14a, Figure 18, Figure 19b, Additional file 3 and Additional file 7. ...[more]

PMID: 31878898

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Exploration for novel inhibitors showing back-to-front approach against VEGFR-2 kinase domain (4AG8) employing molecular docking mechanism and molecular dynamics simulations.

Project description:BACKGROUND:Angiogenesis is a process of formation of new blood vessels and is an important criteria demonstrated by cancer cells. Over a period of time, these cancer cells infect the other parts of the healthy body by a process called progression. The objective of the present article is to identify a drug molecule that inhibits angiogenesis and progression. METHODS:In this pursuit, ligand based pharmacophore virtual screening was employed, generating a pharmacophore model, Hypo1 consisting of four features. Furthermore, this Hypo1 was validated recruiting, Fischer's randomization, test set method and decoy set method. Later, Hypo1 was allowed to screen databases such as Maybridge, Chembridge, Asinex and NCI and were further filtered by ADMET filters and Lipinski's Rule of Five. A total of 699 molecules that passed the above criteria, were challenged against 4AG8, an angiogenic drug target employing GOLD v5.2.2. RESULTS:The results rendered by molecular docking, DFT and the MD simulations showed only one molecule (Hit) obeyed the back-to-front approach. This molecule displayed a dock score of 89.77, involving the amino acids, Glu885 and Cys919, Asp1046, respectively and additionally formed several important hydrophobic interactions. Furthermore, the identified lead molecule showed interactions with key residues when challenged with CDK2 protein, 1URW. CONCLUSION:The lead candidate showed several interactions with the crucial residues of both the targets. Furthermore, we speculate that the residues Cys919 and Leu83 are important in the development of dual inhibitor. Therefore, the identified lead molecule can act as a potential inhibitor for angiogenesis and progression.

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