Regresar

Considering the molecular conformational flexibility in QSAR studies

Abstract:

Conformational flexibility is a crucial aspect to be considered from the molecular structure for obtaining pbkp_redictive quantitative structure-property relationships models. We develop two simple algorithms that are based in the stepwise inclusion procedure and the replacement method, which introduce conformational flexibility in two different ways: (i) by an iterative method and (ii) by taking into account the descriptor values of all the conformations at once. We apply such algorithms to pbkp_redict the apparent second order inactivation rate constant for different serine protease inhibitors based on the 1,2,5-thiadiazolidin-3-one 1,1-dioxide scaffold, and also to structurally heterogeneous inhibitors of the angiotensin converting enzyme. Present approach improves the results obtained by both the stepwise inclusion technique and the replacement method.