A computational study has been performed on a series of 55 compounds having (S)-N-(3-(N-(cyclopean- tylmethyl)substituted-phenylsulfonamido)-2-hydroxypropyl)acetamide backbone as HIV-1 protease inhibitors. Various com...A computational study has been performed on a series of 55 compounds having (S)-N-(3-(N-(cyclopean- tylmethyl)substituted-phenylsulfonamido)-2-hydroxypropyl)acetamide backbone as HIV-1 protease inhibitors. Various combinations of these specific inhibitors fragments were formed by breaking them at central alicyclic single bonds, while retaining the core. Standard Topomer 3D models were automatically constructed for each fragment, and a set of steric and electrostatic fields was generated for each set of topomers. The models generated showed r2 of 0.811 and crossvalidated r2 (q2) of 0.608. The other method used were Quasar and Raptor based on receptor-modelling concept (6D-QSAR) and this explicitly allows for the simulation of the induced fit, that yielded r2 of 0.574, cross-validated r2 (q2) of 0.504 and predictive r2 (q2) of 0.895 averaged over 200 models. This study has suggested the various type of substituent that can be attached to the core. The information obtained from these 3-D contour maps can be used for the design of amprenavir analogs possessing better protease inhibitory activity.展开更多
文摘A computational study has been performed on a series of 55 compounds having (S)-N-(3-(N-(cyclopean- tylmethyl)substituted-phenylsulfonamido)-2-hydroxypropyl)acetamide backbone as HIV-1 protease inhibitors. Various combinations of these specific inhibitors fragments were formed by breaking them at central alicyclic single bonds, while retaining the core. Standard Topomer 3D models were automatically constructed for each fragment, and a set of steric and electrostatic fields was generated for each set of topomers. The models generated showed r2 of 0.811 and crossvalidated r2 (q2) of 0.608. The other method used were Quasar and Raptor based on receptor-modelling concept (6D-QSAR) and this explicitly allows for the simulation of the induced fit, that yielded r2 of 0.574, cross-validated r2 (q2) of 0.504 and predictive r2 (q2) of 0.895 averaged over 200 models. This study has suggested the various type of substituent that can be attached to the core. The information obtained from these 3-D contour maps can be used for the design of amprenavir analogs possessing better protease inhibitory activity.
