title: Molecular recognition pattern of cytotoxic alkaloid vinblastine with multiple targets.
abstract: Vinblastine (VLB), a cytotoxic alkaloid is used extensively against various cancer types and the crystal structure of its tubulin complex is already known. Multitarget affinity of vinblastine has been investigated and the nature of binding with biological receptors namely, duplex DNA and Human serum albumin (HSA) has been compared to the binding characteristics of its known complex with natural high affinity receptor tubulin using molecular docking and QM-MM calculations. VLB is found to interact with DNA as well as HSA protein, though, with weaker affinity as compared to tubulin. Analysis of various docked complexes revealed that the H-bonds and cation-pi bonds do not have significant contribution to the binding interactions and despite its large size, VLB remains in relaxed conformation and fits in the hydrophobic regions on the receptors.
authors.affiliation: Department of Chemistry, University of Rajasthan, Jaipur, India. Electronic address: prateekpandya@gmail.com.
authors.forename: Prateek
authors.initials: P
authors.lastname: Pandya
authors.affiliation: Department of Chemistry, University of Rajasthan, Jaipur, India. Electronic address: lokeshmittal24@gmail.com.
authors.forename: Lokesh Kr
authors.initials: LK
authors.lastname: Agarwal
authors.affiliation: Department of Chemistry, University of Rajasthan, Jaipur, India. Electronic address: guptaniilima@gmail.com.
authors.forename: Neelima
authors.initials: N
authors.lastname: Gupta
authors.affiliation: Physical Chemistry Division, CSIR-National Chemical Laboratory, Pune, India. Electronic address: s.pal@ncl.res.in.
authors.forename: Sourav
authors.initials: S
authors.lastname: Pal
mesh_terms: D004247:DNA / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D011485:Protein Binding; D012709:Serum Albumin / Q000737:chemistry / Q000378:metabolism; D014404:Tubulin / Q000737:chemistry / Q000378:metabolism; D014747:Vinblastine / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D012709:Serum Albumin; D014404:Tubulin; D014747:Vinblastine; D004247:DNA
keywords: Drug–DNA interactions; Drug–protein binding; Human serum albumin; Molecular docking; Multitarget affinity; QM–MM calculation; Vinblastine