An integrated computational workflow for efficient and quantitative modeling of renin inhibitors.
A new integrated computational workflow that couples the strength of the molecular overlay methods to achieve rapid and automated alignments along with 3D-QSAR techniques like CoMFA and CoMSIA for quantitative binding affinity prediction is presented. The results obtained from such techniques are compared with rule-based Topomer CoMFA method, where possible. The developed 3D-QSAR models were prospectively used to predict the affinities of new compounds designed through R-group deconvolution starting from the core chemical scaffold and subsequent virtual combinatorial library enumeration. The general applicability of the seamless in silico modeling workflow is demonstrated using several datasets reported for small molecule inhibitors of renin.
Molecular Innovative Therapeutics, Sanofi US, PO Box 6800, 1041, US Route 202-206, Bridgewater, NJ 08807, USA. govisubra66@gmail.com
Govindan
G
Subramanian
Shashidhar N
SN
Rao
D001665:Binding Sites; D003198:Computer Simulation; D016208:Databases, Factual; D006801:Humans; D017434:Protein Structure, Tertiary; D021281:Quantitative Structure-Activity Relationship; D012083:Renin / Q000378:metabolism; D054852:Small Molecule Libraries / Q000737:chemistry*; D012984:Software; D000092502:Renin Inhibitors
D012083:Renin; D054852:Small Molecule Libraries; D000092502:Renin Inhibitors