Generation of virtual combinatorial libraries of compounds

Abstract

The present invention provides methods for the generation of virtual libraries of compounds. These compounds are generated in silico. The present invention encompasses methods for tracking the addition of fragments, use of reagents, and transformations performed. Further, methods for interfacing the information necessary to generate libraries of compounds with instrumentation that conducts the actual synthesis of the compounds are provided. Also provided are methods for the in silico docking of the library compounds to identified target molecules of interest.

What is claimed is:  
     
         1 . A method of generating a virtual library of compounds in silico comprising: 
 selecting in silico a group of related fragments, each of said fragments constituting a part of said compounds, each of said related fragments having at least one attachment site;    selecting in silico at least one further fragment having at least one attachment site; and    linking in silico said further fragment to said related fragments by connecting the attachment site of said further fragment to the attachment site of said related fragments to generate said virtual library of compounds.    
     
     
         2 . A method of generating a virtual library of compounds in silico comprising: 
 selecting in silico a first fragment, said first fragment constituting a part of said compounds and having at least one attachment site;    selecting in silico a group of related fragments, each of said group of related fragments having at least one attachment site; and    linking in silico each of said group of related fragments to said first fragment by connecting the attachment site of each of said group of related fragments to the attachment site of said first fragment to generate said virtual library of compounds.    
     
     
         3 . A method of generating a virtual library of compounds in silico comprising: 
 selecting in silico a first group of related fragments, each of said first group of related fragments constituting a part of said compounds and having at least one attachment site;    selecting in silico a further group of fragments, each of said further group of fragments having at least one attachment site; and    linking in silico each of said first group of related fragments to each of said further group of fragments by connecting the attachment site of each of said first group of related fragments to the attachment site of each of said further group of fragments to generate said virtual library of compounds.    
     
     
         4 . The method of    claim 1    wherein each of said fragments is introduced in silico into said compounds by the use a corresponding reagent.  
     
     
         5 . The method of    claim 2    wherein each of said fragments is introduced in silico into said compounds by the use a corresponding reagent.  
     
     
         6 . The method of    claim 3    wherein each of said fragments is introduced in silico into said compounds by the use a corresponding reagent.  
     
     
         7 . A method of identifying in silico each compound of a virtual library of compounds comprising: 
 dissecting said compounds into fragments; and    identifying each of said fragments in terms of a transformation wherein said transformation is a one to one link between the fragment and a reagent used to introduce said fragment into a compound.    
     
     
         8 . The method of    claim 7    wherein said transformation is further associated with auxiliary reagents or reaction conditions.  
     
     
         9 . A method of generating a virtual library of compounds in silico comprising: 
 dissecting said compounds into fragments;    representing each of said fragments in silico as a transformation wherein each transformation is a one to one link between a fragment and a reagent used to introduce said fragment into one of said compounds;    selecting in silico a first group of said fragments, each of said first group of fragments constituting a part of said compounds, each of said first group fragments having at least one attachment site;    selecting in silico at least one further fragment having at least one attachment site; and    linking in silico said further fragment to said first group of fragments by connecting the attachment site of said further fragment to the attachment site of said members of said first group of fragments to generate said virtual library of compounds.    
     
     
         10 . A method of generating a virtual library of compounds in silico comprising: 
 dissecting said compounds into fragments;    representing each of said fragments in silico as a transformation wherein each transformation is a one to one link between a fragment and a reagent used to introduce said fragment into one of said compounds;    selecting in silico a fragment, said first fragment constituting a part of said compounds, said first fragment having at least one attachment site;    selecting in silico at group of further fragments each having at least one attachment site; and    linking in silico said group of further fragments to said first fragment by connecting the attachment site of said group of further fragments to the attachment site of first fragment to generate said virtual library of compounds.    
     
     
         11 . A method of generating a virtual library of compounds in silico comprising: 
 dissecting said compounds into fragments;    representing each of said fragments in silico as a transformation wherein each transformation is a one to one link between a fragment and a reagent used to introduce said fragment into one of said compounds;    selecting in silico a first group of said fragments, each of said first group of fragments constituting a part of said compounds, each of said first group fragments having at least one attachment site;    selecting in silico at group of further fragments each having at least one attachment site; and    linking in silico at least some of the members of said group of further fragments to least some of members of said first group of fragments by connecting the attachment site of the members of said further fragments to the attachment site of said members of said first group of fragments to generate said virtual library of compounds.    
     
     
         12 . A method of identifying in silico each compound of a virtual library of compounds comprising: 
 dissecting said compounds into fragments;    adding said fragments together in sequential synthesis rounds; and    tracking the addition of fragments of said compounds.    
     
     
         13 . A method of identifying in silico each compound of a virtual library of compounds comprising: 
 dissecting said compounds into fragments;    representing each of said fragments in silico as a transformation wherein each transformation is a one to one link between a fragment and a reagent used to introduce said fragment into one of said compounds;    adding said transformations together in sequential synthesis rounds; and    tracking transformations in silico.    
     
     
         14 . A method of storing information about the member compounds of a virtual library of compounds comprising: 
 dissecting each of said compounds into fragments;    linking together the fragments of each of the compounds; and    tracking the sequence of linkage for each compound.    
     
     
         15 . The method of    claim 14    further including: 
 grouping two or more compounds of said library together to form a mixture; and  
 linking together the tracked information of each of the members of said mixture.  
 
     
     
         16 . The method of    claim 14    further including: 
 grouping two or more compounds of said library together to form a mixture;  
 grouping a further two or more compounds of said library together to form a further mixture;  
 linking together the tracked information of each of the members of said mixture; and  
 linking together the tracked information of each of the members of said further mixture.  
 
     
     
         17 . A method of storing information about member compounds in a virtual library of compounds comprising: 
 dissecting said compounds into fragments;    representing each of said fragments as a transformation wherein each transformation is a one to one link between a fragment and a reagent used to introduce said fragment into one of said compounds;    linking together the transformations of each of the compounds; and    tracking the sequence of linkage for each compound.    
     
     
         18 . The method of    claim 17    further including: 
 grouping two or more compounds of said library together to form a mixture; and  
 linking together the tracked information of each of the members of said mixture.  
 
     
     
         19 . The method of    claim 17    further including: 
 grouping two or more compounds of said library together to form a mixture;  
 grouping a further two or more compounds of said library together to form a further mixture;  
 linking together the tracked information of each of the members of said mixture; and  
 linking together the tracked information of each of the members of said further mixture.  
 
     
     
         20 . The method of    claim 17    further including: 
 defining each said transformation to further include information related to the synthesis of its fragment from its reagent.  
 
     
     
         21 . A method of storing information about the member compounds of a virtual library of compounds comprising: 
 dissecting each of said compounds into fragments;    grouping two or more compounds of said library together to form a mixture;    linking together the fragments of each of the compounds; and    tracking the sequence of linkage of the members of said mixture.    
     
     
         22 . A method of storing information about the member compounds of a virtual library of compounds comprising: 
 dissecting each of said compounds into fragments;    grouping said compounds of said library into mixtures where each mixture includes two or more member compounds of said library;    linking together the fragments of each of the compounds; and    tracking the sequence of linkage of the members of each said mixture.    
     
     
         23 . A method of storing information about the member compounds of a virtual library of compounds comprising: 
 dissecting each of said compounds into fragments;    representing each of said fragments as a transformation wherein each transformation is a one to one link between a fragment and a reagent used to introduce said fragment into one of said compounds;    grouping two or more compounds of said library together to form a mixture;    linking together the transformation for each of the compounds; and    tracking the sequence of linkage of the members of said mixture.    
     
     
         24 . The method of    claim 23    further including: 
 defining each said transformation to further include information related to the synthesis of its fragment from its reagent.  
 
     
     
         25 . A method of storing information about the member compounds of a virtual library of compounds comprising: 
 dissecting each of said compounds into fragments;    representing each of said fragments as a transformation wherein each transformation is a one to one link between a fragment and a reagent used to introduce said fragment into one of said compounds;    grouping said compounds of said library into mixtures where each mixture includes two or more member compounds of said library;    linking together the transformation for each of the compounds; and    tracking the sequence of linkage of the members of each said mixture.    
     
     
         26 . The method of    claim 25    further including: 
 defining each said transformation to further include information related to the synthesis of its fragment from its reagent.