Computational screening of combinatorial libraries.

We first review existing computational methods with an intrinsic combinatorial feature, then describe a new computational method for screening combinatorial libraries using a recently developed multicopy sampling technique. The new method differs from the existing ones in that it can be used to screen simultaneously an entire library of molecules, instead of the individual molecules in a library. As an example, we have applied the method to study site-directed amino acid substitutions in a protein. After two rounds of library screening, we identified the energetically most stable substitutions along with their optimal conformations from all natural amino acids. In principle, the method is generally applicable to study ligand-host systems.