Bioinformatic analysis of new synthesized benzylidene and indandione derivatives binding to β-amyloid fibrils
Bioinformatic analysis of new synthesized benzylidene and indandione derivatives binding to β-amyloid fibrils
Kimia Ahadi Amandi,1Seyyed Abolghasem Ghadami,2,*Hadi Adibi,3
1. MSc student of biotechnology, Department of Biotechnology, Faculty of Biological Sciences, Alzahra University, Tehran, Iran; 2. Assistant Professor, Department of Biotechnology, Faculty of Biological Sciences, Alzahra University, Tehran, Iran ; 3. Associate Professor, Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
Introduction: Neurodegenerative diseases are some protein structure related diseases. While no applicable treatment is available, scientists have been worked on preventive treatments which acquire early diagnosis. ThT is a probe which has been widely used for diagnosing amyloid structures. While exposing to native protein, ThT shows no significant fluorescence intensity, but when it is placed inside amyloid structure, its fluorescence intensity increases and can be used as a sign of amyloid presence. Considering that positively charged ThT is unable to cross blood brain barrier and its fluorescence intensity will decrease in high concentration of beta amyloids, developing new lack of charge diagnosing agents with higher binding affinity to amyloids has become an issue of interest.
Methods: In this study we have employed some bioinformatic server and software for analyzing binding site and affinity of our compounds to amyloid structures. Compounds’ 2D and 3D structures have been drawed using Chem Draw from Chem Office package. For getting amyloid beta structure we have used (2beg) pdb file from RCSB server. 3D structures have been energy minimized using gromacs software (gromos54a7 forcefield). These optimized forms have been used for docking process in auto dock 4.2 software and final complexes have been made using Lamarckian genetic algorithm.
Results: Our analysis has revealed that synthesized structures have shared same binding site with ThT and shown better binding affinity to beta amyloid structure.
Conclusion: These compounds are suggesting to be novel probes for early diagnosing of neurodegenerative diseases. Further studies including in vivo studies are needed.
Keywords: Beta amyloid, Neurodegenerative diseases, Amyloid structure diagnosis, Thioflavin T