Discovery of Breast Cancer SERM Molecules: Novel Use of Fundamental Quantum Mechanics
Abstract
The background fact of this proposal recognizes that estrogen can cause breast cancer in susceptible women, but has beneficial effects elsewhere. Thus, we need to discover better selective estrogen receptor modulators (SERMs). We propose to discover SERMs through the topology of the electron density. Our rationale hypothesizes that topological pharmacophores exist in the molecular electron density as the fundamental identifying characteristics of SERMs. Our specific aim is to find SERM quantum pharmacophores by calculations of the electron density. We propose to compute the following topology characteristics of the molecular electron density: AIL (atomic interaction line), BCP (bond critical point), BP (bond path) , CP (critical point), CCP (cage critical point) , IAS (inter-atomic surface), (N)NA ((non)nuclear attractor), RCP (ring critical point). Each of the above topological characteristics is uniquely defined by the density, giving it existence at specific geometrical positions in the molecule. Quantum calculation of the electronic density over a drug molecule data base will uncover those topological pharmacophores having geometrical positions & orientations which closely match the cases of known estrogen mimics. This would provide a fundamental new methodology to discover improved SERM drugs, to prevent breast cancer, and promote general health, consonant with National Cancer Institute goals.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2007
- Accession Number
- ADA482813
Entities
People
- Lou Massa
Organizations
- Hunter College