A computer program using Quantum Mechanics to mitigate Breast Cancer
by Lou Massa Hunter College, CUNY.
Overarching Challenge: How does one identify SERM (i.e. estrogen-like) molecules based upon quantum fundamentals? A pharmacophore is that set of properties, carried within a molecular framework, responsible for a drug’s biological activity. We introduce something entirely new, in the search for pharmacophores, viz., quantum mechanical (DFT) electron density critical points. A critical point denotes that the gradient of the electron density is zero. They are easily found by a computer search. And, it is that collection of critical points which overlap in molecules, interacting with a biological target so as to cause its biological response, that constitute quantum mechanical critical point pharmacophores.
Background: It is a unique concept, to discover estrogen mimics through the critical points associated with the quantum mechanical topology of the electron density. Quantum mechanics is invoked via the Hohenberg-Kohn (HK) theorem, the basis of a 1998 Nobel prize, which asserts that all quantum properties of a molecule are encrypted within the electron density. Thus, to know the electron density is to know in principle all quantum properties. By a computer data base search of calculated electron densities, those molecules which contain the critical point pharmacophores of estrogen mimics are revealed. Hypothesis: One can discover pharmacophores from characteristics of the quantum critical points in the electron density of putative drug molecules. The rationale which underlies this proposal is that the topological characteristics of the molecular electron density identify pharmacophores in a fundamental way.
Objective: To find estrogen quantum critical point pharmacophores by computer calculations of the electron density.
Rationale: Our rationale hypothesizes that topological “critical point” pharmacophores exist in the molecular electron density as the fundamental identifying characteristics of estrogen mimics. The estrogen mimetic molecules would seem unrelated electronically, and in that sense their similarities are encrypted within the quantum electron density. What is required is a way to “break the code”, and to uncover thereby the deep similarities within the electronic densities of estrogen mimetic molecules. Thus, we hypothesize quantum topological “critical point” pharmacophores exist in the molecular electron density as the fundamental identifying characteristics of estrogen mimetics.
Methods: The HK theorem guarantees that the quantum information is carried by the electron density. The topology of the electron density decodes the encrypted quantum information, revealing it in chemical language. It follows that the most fundamental pharmacophores are encapsulated in the characteristics which define the quantum topology of the electron density. Critical points, exist at particular geometrical positions within a molecule. Rapid quantum chemistry calculation of the electronic density over a drug molecule data base will uncover those quantum critical point topological pharmacophores having geometrical positions &orientations which closely match the cases of known estrogen mimics.
Relevance: This would allow discovery of improved estrogen mimicking drugs, to prevent breast cancer, and promote good health.
Significance: This suggested computer program would provide a fundamental new methodology to discover improved estrogen drug mimetics, to prevent breast cancer.