Reverse problem formulation approach to molecular design using property operators based on signature descriptors

In this work, an algorithm has been developed for the solution of property based molecular design problems. The recently introduced concept of molecular signature descriptors has been used to design molecules that meet the property targets corresponding to a required process performance. It has been shown that a variety of topological indices (TI) of molecules can be represented in terms of molecular signatures. Signatures can be used to represent different molecular groups if the property targets can be calculated using group contribution models as well. Therefore, the developed algorithm has the ability to combine a variety of property models based on group contribution expressions and topological indices based QSAR/QSPR's to track different property targets in molecular design. This algorithm utilizes molecular property operators formed from signatures for solving the reverse problem of obtaining the molecular structures that satisfy the property targets estimated during the process design step. The principles of graph theory are incorporated to ensure that the design provides feasible molecular structures. Since the molecular operators are formed based on molecular signatures, property models based on different TIs can be represented on the same property platform. Techniques have been developed to describe all TIs with a single signature height. The accuracy of this method depends only on how well the actual property–TI relationships are estimated. Since many TIs can be used to describe each property, this algorithm generally provides reliable results. In addition to physical properties, a wide variety of biological activities can be tracked using the correlations with TIs. This contribution will illustrate the developed methods and highlight their use through a case study.