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ANANBIOANAL - 2010
Pharmaceutical R & D Summit
doi:10.4172/2155-9872.1000057
Multiple Receptor Docking and Dock Pose Clustering as a Tool
for CoMFA and CoMSIA Studies
M.Vijjulatha
Dept. of Chemistry, Osmania University, Nizam College, Hyderabad, India
T
his study was performed on 13 high resolution receptor conformations of HIV-1
protease extracted from protein data bank (1PRO, 1BVG, 1BV9, 1AJX, 1AJV,
1T7K, 1QBR, 1QBS, 1QBU, 1HVR, 1HVH, 1DMP, 1G35). A set of 150 cyclic
urea protease inhibitors with diverse substructures and varied range of inhibition
constants, were docked into the active site of the receptors. After analysis their
binding affinities and interactions with the receptor, the docked poses were clustered
to obtain the best receptor binding conformation. These dock poses from clustering
were used for 3D QSAR analysis, statistically significant CoMFA and CoMSIA
models were generated using 85 molecules in the training set by applying leave one
out cross validation study r2
good internal predictive ability. Based on this information 25 non-cyclic urease
molecules were taken as a test set to check the external predictive ability of these
models. This gave remarkable out come with r2
pred) of 0.54 and 0.67 respectively for CoMFA and CoMSIA indicating
respectively and non-cross validated values of 0.985 and 0.959 were obtained
for CoMFA and CoMSIA respectively. The predictive ability of these models was
determined using a test set of 65 cyclic urease molecules that gave predictive
correlation (r2
cv values of 0.663 and 0.623 for CoMFA and CoMSIA
CoMSIA respectively. This approach is applicable for receptor based alignment for
molecules having varied structural motifs, recommending the increase in accuracy
of 3D QSAR predications for considering diverse scaffolds.
pred of 0.68 and 0.51 for CoMFA and
ANALBIOANAL-2010
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