Extending the drug discovery pipeline to simultaneously-applied chemical agents, and extending the study of evolution to simultaneous mutations, through an ab initio model that relates changes in phenotype to changes in molecular binding interactions

Abstract

Abstract An ab initio model is proposed for extending the search for medicinal drugs to simultaneously-applied chemical agents and extending the study of evolution to simultaneous mutations, through relating the phenotype to molecular binding interaction types. In the case of drug discovery, evaluation of drug candidates for simultaneous use is enabled by incorporating, as design criteria, the effects of coupling between phenotypic properties and binding interactions. This discovery pipeline may yield lead candidates whose collective ability to treat a medical condition exceeds that of independently-applied chemical agents. The pipeline also enables the design of structural adjustments to existing drugs for their simultaneous use, to minimize detrimental side-effects or maximize beneficial side-effects. In the case of evolution, binding interaction types may be identified for simultaneous modification or implementation, by inherited gene mutation, to study transitions from one type of organism to another. Both findings are based on an ab initio model – a multivariate first-principles approach that relates changes in the molecular properties of binding complexes to changes in phenotypic properties, in prokaryotes or eukaryotes. That relationship is a network of binding interaction types whose level of interdependence or coupling is determined through a set of matrix elements. The matrix elements are to be determined for each type of binding interaction using a small set of chemical agents or mutations, and then applied to arbitrary chemical agents or mutations.