A new computational microscope for molecules: High resolution MEDLA images of taxol and HIV-1 protease, using additive electron density fragmentation principles and fuzzy set methods

摘要

Based on the molecular electron density lego assembler (MEDLA) method, a "computational microscope" was developed that generates accurate images of bodies of large molecules at a resolution far exceeding current experimental techniques. The MEDLA "microscope" can be "tuned" to display the high electron density regions of formal chemical bonds; or to show the low density regions of hydrogen bonds and secondary interactions, or to display local shape requirements important in molecular recognition. The power of the method is illustrated by examples of detailed images of taxol, an important anti-cancer agent, and HIV-1 protease, a protein of 1564 atoms. A mathematical framework of the approach, based on fuzzy sets, and the fundamentals of several additional applications of the additive, fuzzy fragmentation principle are presented.