A comparison of crystallographic and DFT optimized geometries on two taxane diterpenoids and docking studies with phospholipase A2

Yadava, Umesh; Gupta, Hariom; Roychoudhury, Mihir

doi:10.1007/s00044-011-9724-z

Cited by 19 publications

(14 citation statements)

References 16 publications

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“…Three‐dimensional (3D) structure of screened green tea bioactive compounds was collected from the PubChem database (https://pubchem.ncbi.nlm.nih.gov) for re‐docking studies by extra precision (XP) docking mode of GLIDE5.8 module in Schrödinger suite . Briefly, 3D structure of ligands was prepared using LigPrep module in Schrödinger suite while optimized by B3LYP/6‐31G** density functional approach . In addition, various conformations were also generated for the selected ligand and minimized in gas phase via employing optimized potentials for liquid simulations (OPLS) force field .…”

Section: Methodsmentioning

confidence: 99%

“…During docking study, protein structure was used as rigid entity while ligand was treated as flexible to find the most feasible interacting resides in the active region. Also, hydrogen bonds, the Van der Waals, polar interactions, coulombic, freezing rotatable bonds, hydrophobic contacts, penalty for buried polar groups, and other factors such as water desolvation energy as well as binding affinity enriching interactions were also considered in the Glide XP scoring protocol . Likewise, known inhibitors as positive control against p23 protein, that is, ailanthone and gedunin were also docked using XP scoring protocol at the selected active site of p23 protein.…”

Section: Methodsmentioning

confidence: 99%

“…32 Briefly, 3D structure of ligands was prepared using LigPrep module in Schrödinger suite 33 while optimized by B3LYP/6-31G** density functional approach. 34 In addition, various conformations were also generated for the selected ligand and minimized in gas phase via employing optimized potentials for liquid simulations (OPLS) force field. 35 Following, unit Van der Waal scaling and partially cutoff at 0.25 value was used for generating ligands electron affinity grid maps.…”

Section: Re-docking and Adme Profilingmentioning

confidence: 99%

“…Also, hydrogen bonds, the Van der Waals, polar interactions, coulombic, freezing rotatable bonds, hydrophobic contacts, penalty for buried polar groups, and other factors such as water desolvation energy as well as binding affinity enriching interactions were also considered in the Glide XP scoring protocol. 34,36 Likewise, known inhibitors as positive control against p23 protein, that is, ailanthone and gedunin were also docked using XP scoring protocol at the selected active site of p23 protein. Following, molecular interaction analysis of receptor-ligand complexes was performed using maestro module in Schrödinger suite.…”

Section: Re-docking and Adme Profilingmentioning

confidence: 99%

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Computational aided mechanistic understanding of Camellia sinensis bioactive compounds against co‐chaperone p23 as potential anticancer agent

Bharadwaj

Lee

Dwivedi³

et al. 2019

J of Cellular Biochemistry

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Co‐chaperon p23 has been well established as molecular chaperon for the heat shock protein 90 (Hsp90) that further leads to immorality in cancer cells by providing defense against Hsp90 inhibitors, and as stimulating agent for generating overexpressed antiapoptotic proteins, that is, Hsp70 and Hsp27. The natural compounds such as catechins from Camellia sinensis (green tea) are also well known for inhibition activity against various cancer. However, molecular interaction profile and potential lead bioactive compounds against co‐chaperon p23 from green tea are not yet reported. To this context, we study the various secondary metabolites of green tea against co‐chaperon p23 using structure‐based virtual screening from Traditional Chinese Medicine (TCM) database. Following 26 compounds were obtained from TCM database and further studied for extra precision molecular docking that showed binding score between −10.221 and −2.276 kcal/mol with co‐chaperon p23. However, relative docking score to known inhibitors, that is, ailanthone (−4.54 kcal/mol) and gedunin ( 3.60 kcal/mol) along with ADME profile analysis concluded epicatechin (−7.013 kcal/mol) and cis‐theaspirone (−4.495 kcal/mol) as potential lead inhibitors from green tea against co‐chaperone p23. Furthermore, molecular dynamics simulation and molecular mechanics generalized born surface area calculations validated that epicatechin and cis‐theaspirone have significantly occupied the active region of co‐chaperone p23 by hydrogen and hydrophobic interactions with various residues including most substantial amino acids, that is, Thr90, Ala94, and Lys95. Hence, these results supported the fact that green tea contained potential compounds with an ability to inhibit the cancer by disrupting the co‐chaperon p23 activity.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Re-docking and Adme Profilingmentioning

confidence: 99%

Section: Re-docking and Adme Profilingmentioning

confidence: 99%

See 2 more Smart Citations

Computational aided mechanistic understanding of Camellia sinensis bioactive compounds against co‐chaperone p23 as potential anticancer agent

Bharadwaj

Lee

Dwivedi³

et al. 2019

J of Cellular Biochemistry

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“…The three-dimensional structures of various isomorphs of PLA2 from a number of sources have been determined and the catalytic residues and substrate binding sites are well characterized in PLA2 enzymes [32,33]. Various ligands have been designed to inhibit their enzymatic function [34][35][36]. Non-steroidal anti-inflammatory drugs have been attributed to their binding to PLA2 [37].…”

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confidence: 99%

Pyrazolo[3,4-d]pyrimidines as inhibitor of anti-coagulation and inflammation activities of phospholipase A 2 : insight from molecular docking studies

2013

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Phospholipase A 2 (PLA2), isolated from Daboia russelli pulchella (Russell's viper), is enzymatically active as well as induces several pharmacological disorders including neurotoxicity, myotoxicity, cardiotoxicity, anti-coagulant, hemolytic, and platelet effects. Indomethacin reduces the effects of anti-coagulant and pro-inflammatory actions of PLA2. Pyrazolo [3,4-d]pyrimidines constitute a class of naturally occurring fused uracils that posses diverse biological activities. The in-silico docking studies of nine pyrazolo[3,4-d]pyrimidine molecules have been carried out with the X-ray crystal structure of Russell's viper PLA2 (PDB ID: 3H1X) to predict the binding affinity, molecular recognition, and to explicate the binding modes, using AUTODOCK and GLIDE (Standard precision and Extra precision) modules, respectively. Docking results through each method make obvious that pyrazolo [3,4-d]pyrimidine molecules with trimethylene linker can bind with both anticoagulation and enzymatic regions of PLA 2 .

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Stabilization of Microtubules by Taxane Diterpenoids: Insight from Docking and MD simulations

2014

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Microtubules are formed from the molecules of tubulin, whose dynamics is important for many functions in a cell, the most dramatic of which is mitosis. Taxol is known to interact within a specific site on tubulin and also believed to block cell-cycle progression during mitosis by binding to and stabilizing microtubules. Along with the tremendous potential that taxol has shown as an anticancer drug, clinical problems exist with solubility, toxicity, and development of drug resistance. The crystal structure of taxane diterpenoids, namely, 10, 13-deacetyl-abeo-baccatin-IV (I), 5-acetyl-2-deacetoxydecinnamoyl-taxinine-0.29hydrate (II), 7, 9-dideacetyltaxayuntin (III), and Taxawallin-K (IV), are very similar to the taxol molecule. Considerable attention has been given to such molecules whose archetype is taxol but do not posses long aliphatic chains, to be developed as a substitute for taxol with fewer side effects. In the present work, the molecular docking of these taxane diterpenoids has been carried out with the tubulin alpha-beta dimer (1TUB) and refined microtubule structure (1JFF) using Glide-XP, in order to assess the potential of tubulin binding of these cytotoxic agents. Results show that all the ligands dock into the classical taxol binding site of tubulin. Taxol shows the best binding capabilities. On the basis of docking energy and interactions, apart from taxol, molecule II has a better tendency of binding with 1TUB while molecule I shows better binding capability with bovine tubulin 1JFF. To validate the binding capabilities, molecular dynamics (MD) simulations of the best docked complexes of ligands with 1JFF have been carried out for 15.0 ns using DESMOND. Average RMSD variations and time line study of interactions and contacts indicate that these complexes remain stable during the course of the dynamics. However, taxol and molecule II prevail over other taxoids.

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A comparison of crystallographic and DFT optimized geometries on two taxane diterpenoids and docking studies with phospholipase A2

Cited by 19 publications

References 16 publications

Computational aided mechanistic understanding of Camellia sinensis bioactive compounds against co‐chaperone p23 as potential anticancer agent

Computational aided mechanistic understanding of Camellia sinensis bioactive compounds against co‐chaperone p23 as potential anticancer agent

Pyrazolo[3,4-d]pyrimidines as inhibitor of anti-coagulation and inflammation activities of phospholipase A 2 : insight from molecular docking studies

Stabilization of Microtubules by Taxane Diterpenoids: Insight from Docking and MD simulations

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