Tran Thi Hoai Van, Minh Quan Pham, Truong Thi Thu Huong, Bui Nguyen Thanh Long, Pham Quoc Long, Le Thi Thuy Huong, George Binh Lenon, Nguyen Thi Thanh Uyen, Son Tung Ngo
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Searching potential GSK-3β inhibitors from marine sources using atomistic simulations.
Glycogen synthase kinase-3 beta, GSK-3β, is one of the most common targets for cancer treatment. Inhibiting the biological activity of the enzyme can lead to the prevention of cancer development. Especially, estimating a new inhibitor for preventing GSK-3β by using natural compounds is of great interest. In this context, the marine compounds were investigated for their ligand-binding affinity to GSK-3β via atomistic simulations. The compounds, including xanalteric acid I, chaunolidone A, macrolactin V, and aspergiolide A, were suggested that can inhibit GSK-3β via molecular docking and steered-MD simulations. Moreover, the potency of these compounds was also confirmed via the perturbation simulations. Furthermore, the toxicity prediction also indicates that these compounds would adopt less toxicity. Therefore, it may be argued that four compounds can play as potential inhibitors preventing GSK-3β. In addition, the residues including Ile62, Val135, Pro136, Arg141, Lys183, Gln185, Asn186, and Asp200 play a crucial role in the GSK-3β binding process.
期刊介绍:
Molecular Diversity is a new publication forum for the rapid publication of refereed papers dedicated to describing the development, application and theory of molecular diversity and combinatorial chemistry in basic and applied research and drug discovery. The journal publishes both short and full papers, perspectives, news and reviews dealing with all aspects of the generation of molecular diversity, application of diversity for screening against alternative targets of all types (biological, biophysical, technological), analysis of results obtained and their application in various scientific disciplines/approaches including:
combinatorial chemistry and parallel synthesis;
small molecule libraries;
microwave synthesis;
flow synthesis;
fluorous synthesis;
diversity oriented synthesis (DOS);
nanoreactors;
click chemistry;
multiplex technologies;
fragment- and ligand-based design;
structure/function/SAR;
computational chemistry and molecular design;
chemoinformatics;
screening techniques and screening interfaces;
analytical and purification methods;
robotics, automation and miniaturization;
targeted libraries;
display libraries;
peptides and peptoids;
proteins;
oligonucleotides;
carbohydrates;
natural diversity;
new methods of library formulation and deconvolution;
directed evolution, origin of life and recombination;
search techniques, landscapes, random chemistry and more;