how to check inhibition constant in autodock vina

#HOW TO CHECK INHIBITION CONSTANT IN AUTODOCK VINA SERIES#

Scientists also looked towards other tau-induced therapies for AD such as tauopathies. Quite a lot of efforts have been made towards finding the cure for AD for the last 20 years against Aβ-based therapeutics including drug identification, and antibody generation but these are not successful. įor understanding the disease mechanism and inhibitor identification, several studies have been done recently. AD is also linked with several autosomal mutations in the genes which are inherited from parents encoding APP, tau protein, and presenilins 1 and 2 (PSEN1 and PSEN2), and these mutations induce the Aβ plaques and NFTs formation. AD showed very complex disease etiology which is characterized by majorly two hallmarks, first is the association of amyloid β plaques which is formed by the abnormal cutting of amyloid precursor protein (APP) while another hallmark is the neurofibrillary tangles (NFTs) being formed by the association of hyperphosphorylated microtubule-associated binding protein (MAPT). There is an urgent need to find treatment and cure for this disease. The impact of the disease is reflected by its rise in incidence rate where one person develops dementia every 3 second globally. The disease showed a very high economic burden on the global society as 1 trillion US$ loss in 2018 was observed while it will double till 2030. According to the World Alzheimer Report of WHO 2018, this number (50 million) for dementia will be tripled (~152 million) by the year 2050, which reflects the seriousness of this disease for mankind. It is the major cause of death in the USA and is ranked 6th in number. Worldwide approximately 50 million people are suffering from some form of dementia in which AD is the most contributing disease (60–70%). The study suggested three compounds (ZINC15968620, ZINC15968622, and ZINC70707119) have great potential to be a drug candidate and can be tested using in vitro and in vivo experiments for further characterization and applications.Īlzheimer’s disease (AD) majorly contributes to dementia and is a lethal neurodegenerative disease. From all these analyses, we have concluded that out of 167,741 compounds, the ZINC15968620, ZINC15968622, and ZINC70707119 can act as lead compounds against HsGSK-3 β to reduce the hyperphosphorylation. Four best compounds were employed for MDS and here predicted RMSD, RMSF, Rg, hydrogen bonds, SASA, PCA, and binding-free energy. All these compounds were re-docked by using Autodock Vina followed by Autodock. From here, we have selected 20 compounds those were good in terms of pharmacokinetic parameters. The resulting analysis of virtual screening suggested that 404 compounds show good binding affinity and can be employed for pharmacokinetic analysis.

We have retrieved a set of compounds ( n=167,741) and screened against GSK-3 β in four sequential steps.

#HOW TO CHECK INHIBITION CONSTANT IN AUTODOCK VINA SERIES#

In this study, we have used a series of computational approaches to find novel inhibitors against GSK-3 β to reduce the TAU hyperphosphorylation. The glycogen synthase kinase 3 beta plays a major role in the hyperphosphorylation of tau protein which forms the neurofibrillary tangles which is a major hallmark of AD. AD is a very complex disease and the drugs available in the market cannot fully cure it. Alzheimer’s disease is a leading neurodegenerative disease worldwide and is the 6th leading cause of death in the USA.

How to check inhibition constant in autodock vina