Traditionally,analog-based molecular modeling schemes cannot take into account protein plasticity,which is of critical importance to accurately model protein-ligand interactions especially when the target protein can adopt a variety of conformations when interacting with structurally diverse small molecules.A novel scheme,in which the prediction model is constructed by assembling a panel of plausible pharmacophore hypotheses (pharmacophore ensemble) to represent various target protein conformations,followed by regression by support vector machine (SVM),has been devised to address protein plasticity and will be introduced.In addition,the accuracy and robustness of prediction models based on PhE/SVM will be demonstrated by a number of examples and comparisons with crystal structures.