Combinatorial-computational-chemoinformatics (C3) approach to finding and analyzing low-energy tautomers

Area of Science:

• Computational chemistry
• Molecular modeling
• Cheminformatics

Background:

• Predicting stable tautomers is vital for molecular modeling and virtual screening.
• Existing methods are reliable for neutral molecules in common solvents but fail for charged species in unusual solvents.

Purpose of the Study:

• To develop a robust method for identifying stable tautomers of challenging molecular systems.
• To address limitations in predicting tautomers for charged molecules in non-aqueous solvents.

Main Methods:

• A three-step approach: combinatorial tautomer generation, energy-based screening using electronic structure methods, and chemoinformatics analysis.
• The hybrid method is termed Combinatorial*Computational*Chemoinformatics (C3).

Main Results:

• Successfully applied the C3 approach to identify stable anionic tautomers of nucleic acid bases.
• Demonstrated the method's efficacy in predicting tautomers for systems lacking sufficient chemical knowledge.

Conclusions:

• The C3 approach offers a reliable solution for determining stable tautomers in complex and esoteric molecular systems.
• This hybrid methodology advances computational chemistry and molecular modeling capabilities.