Drug Designing: Open Access
Open Access

Current progress in structure-based rational drug design marks a new mindset in drug discovery

International Conference and Expo on Drug Discovery & Designing

August 11-13, 2015 Frankfurt, Germany

Val�?¨re Lounnas

Posters-Accepted Abstracts: Drug Des

Abstract :

As the paradigm of serendipity appears to have reached hard operational limitations in the field of drug discovery, there seems
to be a renewed interest for investigating the detail of interactions between the ligands and their receptors. The past decade
has witnessed a paradigm shift in preclinical drug discovery with structure-based drug design (SBDD) making a comeback while
high-throughput screening (HTS) methods have continued to generate disappointing results. This is due to a deficit of information
between identified hits and the many criteria that must be fulfilled in parallel to convert them into preclinical candidates that have a
real chance to become a drug. Although accurate calculations of the free energy of binding are still elusive, receptor structure-based
ligand interaction models may provide a wealth of information sufficient to allow feedback from experimental validation to be
integrated in the model and generate workable information opening for rationally guided alternative proposals in chemical synthesis
and testing plans during lead optimization. Unfortunately, in too many cases effective/operative structure-based models cannot be
successfully elaborated. Although generally not overlooked, SBDD is hindered in practice mainly due to shortage of allocated time,
insufficient expert manpower and dis-synchronization of the collaborative work between modelers and chemists. We propose to
discuss some of the prerequisites and operational conditions when elaborating workable models throughout examples of prototypical
situations covering the current possibilities and limitations of SBDD.