************ The 1st Lab Seminar ***************************************

Title : Toward a new tool of host-ligand recognition: design of new 
        PDE4 inhibitors guided by quantum docking, synthesis and 
        biological evaluation

Speaker : Chantal barberot

Date : Wed. Jun. 4th, 1:30 pm

Place : Seminar room of 4F, Graduate School of Information Science

Abstract :
PDE4 inhibitors are an attractive target for the research of new 
treatment of bronchopulmonary diseases such as asthma and chronic 
obstructive pulmonary disease (COPD). A new inhibitors family based on 
the pyridazinone pattern have been studies using molecular modeling 
(docking: methodological development and application), organic 
synthesis and biological tests.
The development of the molecular docking software AlgoGen1 will be 
presented. AlgoGen (initially created at university of Lorraine in 
2009) is a program which couples a genetic algorithm for the 
conformational search and a protein-ligand energy evaluation at the 
quantum semi-empirical level (while other software do this evaluation 
at a classical level). Thus, some modifications have been made to 
improve its efficiency for the conformational search2 because quantum 
energy calculations are very time consuming. This software was then 
used for evaluation of a set of 22 dimers (typical in biological 
molecular recognition3) as well on seven ligand-protein complexes.
Then, the search of new PDE4s inhibitors will be presented. In this 
part, the synthesis and the biologic evaluation of a few potential 
PDE4 inhibitors will be shown. Then, the AlgoGen software will be used 
to study the structure-activity relationship of these different 
potential inhibitors and will help for the design of new compounds.


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