| چکیده انگلیسی مقاله |
CC chemokine receptors are introduced as integral membrane proteins that particularly attach and respond to cytokines of the CC chemokine family representing one subfamily of chemokine receptors, a large family of G protein-linked receptors. CCR1 is broadly known as the first noticed CC chemokine receptor binding several inflammatory/inducible CC chemokines[1], whereas CCR2 has been distinguished on the surface area of monocytes, activated memory T cells, B cells, and basophils in humans[2]. Another indubitably vital member of CCR family is CCR4 that expressed on Th2 T lymphocytes[3], whilst undoubtedly the most important CC chemokine receptor called CCR5 is expressed on multiple cell types including peripheral blood-derived dendritic cells, CD34+ hematopoietic progenitor cells to name but a few and it is patently defined as an essential coreceptor implicated in susceptibility to HIV-1 infection and disease[4]. The given article illustrates the characterization of molecular features that induce selectivity for inhibition of CCR1, CCR2, CCR4 and CCR5, in which the number of 7294 molecules were collected from Binding Database and 3224 molecular descriptors for each molecule were calculated via Dragon Talete 5.5. Moreover, the best feasible subset of molecular descriptors were selected utilizing Variable Importance in Projection (VIP), providing the opportunity to classify the mentioned targets based on their therapeutic features and activities. Five various classification methods namely PLS-DA, SVM, SKN, KNN and CPANN were used so as to find the relationship amongst molecular structures of chemicals, their activities and selectivities. Generally, the performances of classified models were evaluated according to the statistical parameters derived from the given confusion matrices. Additionally, both dependability and predictability of the conducted models were estimated by the tenfold cross-validation techniques and test sets. The reliable statistical values of the obtained classified molecules can be not only meticulously found handful in order to design brand new drugs with selective inhibitory activities toward CCR1, CCR2, CCR4 and CCR5, but also much more efficacious in pharmaceutical aspects of miscellaneous medical treatments for inflammation, rheumatoid arthritis, cancer and infections resulted in HIV-1 virus. |
