The goal of this project is to provide, to the large community of scientist working in molecular target therapies, a fast and accurate tool capable of obtaining an atomic detailed mechanism of the protein-ligand induced fit, of its recognition process and of the ligand migration. Understanding these aspects is essential to obtain better drugs with the ability, for example, of bypassing drug resistance induced by protein mutations. This resistance mechanism is currently a fundamental process that will be increasing substantially with further development of specific molecular targets. The main ideas are based on state of the art methodologies recently developed in our laboratory capable of describing these processes. PELE, our novel technology based on protein structure prediction algorithms and a Monte Carlo sampling, is capable of describing the all atom dynamical interaction between a protein and a ligand. The proposed objectives includes: 1) Continue the methodological development of PELE, 2) developing automatic protocols for the study of the drug-protein dynamical interaction, and 3) building a web server allowing public use of these development The resulting technology will allow scientist to understand the atomic mechanism for drug delivery, drug resistance, etc., in only few days, approximately in 100 hours of CPU, allowing for a la carte design of improved inhibitors in a timely fast manner (essential when probing hundreds of compounds!). The development of the modelling tools, disseminated and freely accessible by means of a web server, will be conducted at the Barcelona Supercomputing Center, the Spanish national supercomputing center with one of the best computational infrastructures in Europe.
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