Abstract
BACKGROUND
Docking and 3D QSAR studies were performed on Inhibitor of Bacterial DNA gyrase to develop a predictive Common Pharmacophore Hypothesis (CPH). Molecular interaction and binding affinities of these analogues, differing with nucleotides and amino acids are studied are performed.
METHODS
Biological activity is predicted by QSAR approach by relating the set of compounds. QSAR study was applied using PHASE, the docking studies were performed using Glide module and Prime/MM-GB/SA is used for free energy ligand binding calculations.
RESULTS
We obtained high pred_r2 value (pred_r2= 0. 9239), suggesting a significant external predictive ability of the QSAR model. Mutant docking score is -9. 023. In Wild type docking it shows lower binding energy and binding affinity is a decrease so, docking score of wild most dock 26 molecule is - 6.093. Protein shows various sites for molecular interaction, so from MM-GBSA.
CONCLUSION
In the present study, development of predictive hypothesis (CPH) for 4-substituted cyclobutylphenyl quinoline derivatives and CPH were generated and results were interpreted on a developed model containing five features gives good and predictive statistical significance. Docking studies explained hydrogen bonding, pi-pi stacking with deoxy-ribonucleotide and with Ala 1120 and positive charge with deoxyribonucleotide. MM-GBSA explains the binding affinity of most docked ligand with protein.
TY - JOUR
T1 - Docking and 3D QSAR Studies on Substituted Cyclobutylphenyl Quinoline Derivatives as Inhibitors of Bacterial DNA Gyrase.
AU - Wani,Rucha R,
AU - Chaudhari,Hemchandra K,
PY - 2017/07/19/received
PY - 2018/01/05/revised
PY - 2018/05/14/accepted
PY - 2018/5/17/pubmed
PY - 2019/1/12/medline
PY - 2018/5/17/entrez
KW - 2XCS
KW - 3D-QSAR
KW - CPH
KW - DC
KW - DG
KW - Docking
KW - PHASE.
SP - 322
EP - 337
JF - Current computer-aided drug design
JO - Curr Comput Aided Drug Des
VL - 14
IS - 4
N2 - BACKGROUND: Docking and 3D QSAR studies were performed on Inhibitor of Bacterial DNA gyrase to develop a predictive Common Pharmacophore Hypothesis (CPH). Molecular interaction and binding affinities of these analogues, differing with nucleotides and amino acids are studied are performed. METHODS: Biological activity is predicted by QSAR approach by relating the set of compounds. QSAR study was applied using PHASE, the docking studies were performed using Glide module and Prime/MM-GB/SA is used for free energy ligand binding calculations. RESULTS: We obtained high pred_r2 value (pred_r2= 0. 9239), suggesting a significant external predictive ability of the QSAR model. Mutant docking score is -9. 023. In Wild type docking it shows lower binding energy and binding affinity is a decrease so, docking score of wild most dock 26 molecule is - 6.093. Protein shows various sites for molecular interaction, so from MM-GBSA. CONCLUSION: In the present study, development of predictive hypothesis (CPH) for 4-substituted cyclobutylphenyl quinoline derivatives and CPH were generated and results were interpreted on a developed model containing five features gives good and predictive statistical significance. Docking studies explained hydrogen bonding, pi-pi stacking with deoxy-ribonucleotide and with Ala 1120 and positive charge with deoxyribonucleotide. MM-GBSA explains the binding affinity of most docked ligand with protein.
SN - 1875-6697
UR - https://www.unboundmedicine.com/medline/citation/29766821/Docking_and_3D_QSAR_Studies_on_Substituted_Cyclobutylphenyl_Quinoline_Derivatives_as_Inhibitors_of_Bacterial_DNA_Gyrase_
DB - PRIME
DP - Unbound Medicine
ER -
