Methods for predicting an active set of compounds having alternative cores, and drug discovery methods involving the same

Abstract

A system, device, and method for predicting an active set of compounds that bind to a biomolecular target is disclosed. The system and device contain modules allowing for the prediction of an active set of compounds. A core identification module can identify the core of an initial lead compound. A core hopping module is used to identify potential lead compounds having different cores compared to the core of an initial lead compound. A scoring module can use computational techniques to calculate the relative binding free energy of each identified potential lead compound. An activity prediction module can use the relative binding free energy calculations to predict an active set of compounds that bind to the biomolecular target. Empirical analysis can be used to inform the accuracy and completeness of the predicted active set of compounds.

What is claimed is: 
     
         1 . A method of identifying a plurality of potential lead compounds, the method comprising the steps of:
 analyzing, using a computer system, an initial lead compound known to bind to a biomolecular target, the analyzing comprising partitioning the initial lead compound into atoms defining a lead compound core and atoms defining a lead compound non-core;   identifying, using the computer system, a plurality of alternative cores to replace the lead compound core in the initial lead compound, thereby generating a plurality of potential lead compounds each having a respective one of the plurality of alternative cores;   calculating, using the computer system, a difference in binding free energy between the initial lead compound and each potential lead compound; and   predicting, using the computer system, whether each potential lead compound will bind to the biomolecular target and identifying a predicted active set of potential lead compounds based on the prediction.