Activity modeling and simulation of bacterial efflux pump inhibitors based on advanced laser methods
PN-II-PT-PCCA-2011-3.1-1350
2012
Activity I. Drug characterization studies for EPI activity assessment
Activity I.1: 3: Irradiation of chemical compounds (putative EPI drugs) and their spectral characterization. Analysis of efflux pumps inhibitory activity of studied chemical compounds.
Activity I.2: Development of a high performance computing platform for bioinformatics. Update on the software and libraries for bioinformatics and protein structure prediction.
Activity I.3 : Survey of recent work on bacterial MDR and EPIs testing protocols. Development of protocols for testing drug-bacterial EPI interactions on laboratory animal models.
2013
Activity II: Drug modeling and EPI mechanisms analysis
Activity II.1: 3: Performing IR absorption measurements before and after laser irradiation of EPI drugs, development of models for EPI drug activity and investigation of drug-efflux pump interaction models.
Activity II.2: Development of a high performance computing platform for molecular modeling, molecular dynamics and computational prediction of the effects of drugs on the bacterial efflux pumps at the molecular level.
Activity II.3: Application of chemical compounds with predicted EPI effect on rabbit eyes infected with strains of bacteria and differential analysis of non-irradiated and irradiated drugs effects.
2014
Activity: Simulation of drug interaction with bacterial EPs I
Activity III.1: 3: Measurement of IR and Raman spectra of drugs with predicted EPI effect before and after exposure to laser beams; development of methods for the analysis of vibrational spectra of drugs (irradiated and non-irradiated); development of methods for the analysis of the relationship between structure and activity of putative EPI drugs.
Activity III.2: Developing computational models for EPI activity of drugs. Performing simulations of efflux pumps inhibitory processes on HPC platform using molecular modeling software; maintaining access to molecular modeling and electronic structure computation software.
Activity III.3 : Application of selected phenothiazines and quinazolines on laboratory rabbit eyes infected with bacterial strains and differential diagnosis of results.
2015
Activity IV. Simulation of drug interaction with bacterial EPs II.
Activity IV.1: Vibrational spectroscopy analysis for EPI activity estimation of drugs: quinazolines or phenothiazines.
Activity IV.2: : Implementation of VLS algorithms and methods, simulation of interaction processes on HPC platform using molecular modeling software on quinazolines or phenothiazines; performing VLS tests and providing access to the electronic and molecular structures computing software.
Activity IV.3 : Quinazolines or phenothiazines application on laboratory rabbit eyes which are infected with Gram-positive or Gram-negative bacteria and results synthesis.
2016
Activity V :
Validation of predicted drug pathogen interactions
