Establish And Evaluation Of Modelling MDCK Cell Permeability In Silico

BACKGROUND AND OBJECTIVIESIn this thesis we collected MDCK cell permeability data from journal database and chemoinfromatics database using MOE2011, caculated molecular descriptors, established and evaluated a MDCK cell permeability model. This paper aims to establish a roboust and precise QSAR model of MDCK cell permeability, offer a tool to screen compounds MDCK cell permeability in silico in early drug discovery and develop period. METHODS AND RESULTS1. Estalishment of MDCK cell permeability modelIn this chapter MDCK cell permeability data were collected,transformed and input.Using MOE2011chemical structure was energy minimized. Caculate the molecular descriptors (including2D molecular and3D molecular descriptors), and spilt into training and test set randomly. Remove the duplication, involve descriptors, and nearly constant descriptors, then screen the variability using GA-PLA, finally remain10descriptors. Create a liner model using MLR. The root mean square error (RMSE) is0.43207,and the correlation coefficient (R2) is0.86628.2. Evaluation of MDCK cell permeabiltity modelIn this chapter the MDCK cell permeability model was evaluated using LOO,5fold validation, Y randomize, test set validation and application domain in MOE2011AutoQSAR moduel. The outcome is below:LOO RMSE=0.52019; LOO R2=0.80768;5fold RMSE=0.52019; Z-SCORE VS RANDOM=9.64223; q2=0.77115.CONCLUSIONSThis theis estabish a MDCK cell permeability model:-logPapp=-2.81270+1.03126*PC+-0.01293*PEOE_VSA+1+0.41244*dipoleX+5.31619 *glob-0.10999*opr_brigid+2.45322*vsurf_CW1+0.02388*vsurf_D8+1.05636*vsurfJEDminl-0.04246*vsurf_Wp4+0.02238*SMR_VSA4. After LOO validation,5fold validation, Y randomize validation and application domain, the model acts well. So the model is robust. This paper offers an advise to compounds to screen MDCK cell permeability in drug discovery and develop.