Computational evaluation of small molecule inhibitors of RGS4 to regulate the dopaminergic control of striatal LTD

Parkinson's disease is a neurodegenerative disease which is the result of the degradation of the dopaminergic neurons in the substantia nigra pars compacta, leading to a disregulation of thalamocortical circuits. Traditional treatment involves the use of levodopa which increases the dopamine level in the striatum. There is a need for alternative non-dopamine therapy to prevent the side effects of the conventional drugs used. Recently small molecule inhibitors of RGS have become the prime candidates in studies related to regulating RGS by binding to its allosteric site and thus changing its structure. Through the docking studies we observed that these small molecule modulators of RGS4 make stable complexes with RGS4 when compared to native RGS4. The Gq[alpha]-RGS4-drug complexes are less stable. The increase in flexibility of the RGS4-drug complex could be the reason for the inability of the RGS4-drug complex to bind to the G protein. In our docking results, CCG63802 formed the most promising drug as a RGS4 inhibitor as it formed the most stable complex with RGS4 and also formed the least stable complex, Gq[alpha]-RGS4-CCG63802 complex. In our studies we evaluated the therapeutic potential of the small molecule inhibitors to provide a prospective treatment for Parkinson's disease

Insight into Nek2A activity regulation and its pharmacological prospects

Nek2A is an essential component of cell cycle progression. It regulates the reorganization of the microtubule network at the G2/M transition and controls the centriole-centriole linkage of the cells entering mitosis. The overexpression of Nek2A coding gene has been widely reported in several cancer-associated disorders. In order to design a potent inhibitor and to control its expression mechanism, it is important to understand the structural orientation and the underlying molecular mechanisms associated with its activity regulation. In this study we have summarized the important information that will help in understanding the functional and activity regulation of Nek2A splice variants, which will further facilitate in designing a potent inhibitor against the cancer associated cases. We have also presented previously reported studies on the domain specifications and inhibitor biosynthesis that provide an insight into its specific target residue regions for developing active and more potent inhibitors

Sequencing Closterium moniliferum: future prospects in nuclear waste disposal

Genome sequencing can play a vital role in health and several other domains such as in nuclear outflow related environmental issues. The power of information derived out of sequencing has been used in the field of health care, evolutionary studies and for better understanding of the biological framework of life. Through the recent advancements in sequencing studies, now the researchers are aiming to use its power in non conventional areas. Here we have discussed on the importance of sequencing the Closterium moniliferum genome which will prove to be a future endeavour in nuclear cleanup and radioactive waste disposal