Drug Designing: Open Access
Open Access
ISSN: 2169-0138
ISSN: 2169-0138
Cosimo G. Fortuna, Laura Goracci1, Rosario Musumeci and Andrea Pace
Scientific Tracks Abstracts: Drug Design
Chemoinformatic strategies possess great potentialities in modelling the interactions between biopolymers and ligands. Molecular recognition plays in fact a fundamental role in drug-receptor interactions. Due to the lack of pharmacological targets, in previous studies [1] we adopted a Virtual Receptor Site (VRS) approach, where ligands interact with a complex receptor of unknown structure, aimed at identifying pieces of the structure which could be valuable for improving the antibacterial activity. In the design of new drugs it is also very important that they exhibit ADME (Adsorption, Distribution, Metabolism, Elimination) properties warranting an acceptable bioavailability. For this purpose, a new method, called VOLSURF [2], able to correlate 3D molecular structures with physico-chemical properties, and highly efficient in predicting the biological activities, appears to be appropriate. In this context, we adopted a recently developed algorithm called Fingerprints for Ligands and Proteins (FLAP) that can be used to describe proteins and ligands based on a common reference framework [3]. By means of all these chemoinformatic tools, we studied the interactions between synthetically accessible compounds and the crystallographic structure of Linezolid binding protein to identify a scaffold that we could modify introducing different substituents to improve the in vitro antibacterial activity. Molecular modeling was performed using two different approaches, based on FLAP and Amber software. A comparison of the binding pose of our compounds with respect to the crystallographic pose of linezolid is reported. The two methods independently suggest that the in vitro activity could be ascribed to stability and metabolic reasons rather than to a different binding mode with the protein.