Method, system, and tool for creating, filtering, and selecting molecules in drug design for therapeutic effects

A method for discovering new bioisosteres of a molecule, the method comprising:

• selecting a first molecule of interest having an amide group as a first bioisostere;
• replacing the amide group of the first molecule of interest with a 1,4-substituted or 1,5-substituted 1,2,3-triazole group as a second bioisostere to obtain a second molecule with the second bioisostere;
• completing quantum mechanics (QM) simulations to obtain optimized geometries having no imaginary frequencies for the first and second molecules containing the first and second bioisosteres as docked in a receptor or as not docked in a receptor;
• evaluating average electron density (AED) values, using an average electron density tool, corresponding to the first and second bioisosteres in the first and second molecules as docked in the receptor;
• confirming experimentally observed bioisosterism between the 1,4-substituted or 1,5-substituted 1,2,3-triazole group and the amide group based on the calculated AED values;
• identifying those calculated AED values equivalent between the first and second bioisostere, wherein the equivalent calculated AED values have a difference of no more than 10% between one another;
• identifying additional sets of atoms having calculated AED values corresponding to the calculated AED values equivalent between the first and second bioisosteres, wherein the corresponding calculated AED values have a difference of no more than 10% from the equivalent calculated AED value of the first bioisostere;
• computationally replacing the amide group of the first molecule of interest with one of the identified additional sets of atoms to obtain a third molecule with a third bioisostere;
• and
• screening the third molecule with the third bioisostere to determine whether the third molecule with the third bioisostere is a drug candidate having a desired biological activity.