In silico identification of potential inhibitors for human aurora kinase b

Cell cycle progression through mitosis and meiosis involves regulation by serine/threonine kinases from the aurora family. Aurora kinase b (Aurkb) is mainly involved in the proper segregation of chromosomes during mitosis as well as meiosis. However, over expression of Aurkb leads to the unequal distribution of genetic information creating aneuploid cells, a hallmark of cancer. Thus, Aurkb can be used as an effective molecular target for computer-aided drug discovery against cancer. Existing Aurkb inhibitors are less efficient, hence an in silico work was carried out to identify novel potent inhibitors. Three published inhibitors azd1152, zm447439 and N-(4-{[6-methoxy-7-(3-morpholin-4-ylpropoxy) quinazolin- 4-yl] amino} phenyl) benzamide were subjected to high throughput virtual screening of over 1 million entries from a ligand info meta database, to generate a 1161 compound library. The crystal structure was optimized and energy was minimized applying an OPLS force field in Maestro v9.0. Molecular docking using Glide was performed to predict the binding orientation of the prepared ligand molecule into a grid of 20*20*20 Å created around the centroid of the optimized human Aurkb protein. Nine lead molecules with good binding affinity with human Aurkb were identified. In silico pharmacokinetics study for these nine lead molecules has shown no ADME violation. Analysis of lead ‘1’- human Aurkb docking complex has revealed a XP Gscore of -10.20 kcal/mol with a highly stabilized hydrogen bond network with Asp218 and Ala157 and good Van der wall interactions. The docking complex coincides well with the native co- crystallized human Aurkb and inhibitor zm447439 complex. Thus, lead 1 would be highly useful for developing potential drug molecules for the treatment of cancer

Which governs - the relationship or the contract?

According to the transaction cost economics literature, a firm’s external contractual relationships must be ‘fit for purpose’. What is a ‘fit for purpose’ contractual relationship should not be a normative decision, but an objective one, to be made with regard to achieving transaction cost efficiency, while defending the core competencies of the firm. Data from a Hong Kong case study is used to examine whether or not the client’s choice of contractual relationship is ‘fit for purpose’ and also to evaluate the impact of such a choice. The findings suggest that maintaining a relationship of high quality as a strategic policy not only reduces recourse to the contract but, also improves the quality and predictability of project performance and, is an antidote to ill-aligned contractual elements. These findings lend support to the growing trend towards relationship or relational contracting in construction

Organic Cotton Crop Guide - A manual for practitioners in the tropics

Designed primarily as a reference manual for extension workers and farmers, the Organic Cotton Crop Guide provides comprehensive practical know-how on organic cotton production in the tropics. The guide covers all relevant aspects from soil preparation and variety selection over crop nutrition and pest management to the economic performance of organic cotton farming

Book Review

The future of the academic journa

Paper-based diagnostics for COVID-19 developed by CSIR-IGIB

28-29On 3rd April, CSIR achieved a breakthrough in its ongoing war against devastating coronavirus as CSIR-IGIB developed a low-cost diagnostic paper-based kit that can accurately test COVID-19 samples

Science Communication for Transforming India

Science films and science literature play a very important role in science communication, said Dr. Harsh Vardhan, Hon’ble Minister of Science & Technology, Earth Sciences and Environment, Forest & Climate Change. He also added that he dreamt of a day when science films would be the first choice of entertainment of the common man. Dr. Harsh Vardhan was speaking at the conclusion of the International Science Literature & Film Festival held at the Atal Bihari Vajpayee Scientific Convention Centre, Lucknow during 6-8 October 2018

In silico identification of potential inhibitors for human aurora kinase b

Cell cycle progression through mitosis and meiosis involves regulation by serine/threonine kinases from the aurora family. Aurora kinase b (Aurkb) is mainly involved in the proper segregation of chromosomes during mitosis as well as meiosis. However, over expression of Aurkb leads to the unequal distribution of genetic information creating aneuploid cells, a hallmark of cancer. Thus, Aurkb can be used as an effective molecular target for computer-aided drug discovery against cancer. Existing Aurkb inhibitors are less efficient, hence an in silico work was carried out to identify novel potent inhibitors. Three published inhibitors azd1152, zm447439 and N-(4-{[6-methoxy-7-(3-morpholin-4-ylpropoxy) quinazolin- 4-yl] amino} phenyl) benzamide were subjected to high throughput virtual screening of over 1 million entries from a ligand info meta database, to generate a 1161 compound library. The crystal structure was optimized and energy was minimized applying an OPLS force field in Maestro v9.0. Molecular docking using Glide was performed to predict the binding orientation of the prepared ligand molecule into a grid of 20*20*20 Å created around the centroid of the optimized human Aurkb protein. Nine lead molecules with good binding affinity with human Aurkb were identified. In silico pharmacokinetics study for these nine lead molecules has shown no ADME violation. Analysis of lead ‘1’- human Aurkb docking complex has revealed a XP Gscore of -10.20 kcal/mol with a highly stabilized hydrogen bond network with Asp218 and Ala157 and good Van der wall interactions. The docking complex coincides well with the native co- crystallized human Aurkb and inhibitor zm447439 complex. Thus, lead 1 would be highly useful for developing potential drug molecules for the treatment of cancer

Information Seeking Behaviour Among Distance Education Learners in Relation to Gender, Location and Education

The part of self-efficacy in diverse tasks and learning environment has mainly been emphasized, exclusively in searching for information by the distance learners. The study conducted survey with the distance students of Bangalore University forms the subject matter of this research. Questionnaires were distributed personally during the contact classes at the study centers and postgraduate departments of the university and was able to retrieve maximum quantity i.e., 1445 (93.22%) of the filled in questionnaires from the distributed 1550 questionnaires of the sample population. The Major objective of the study is to identify the needs and address the behavioural pattern of distance learners of this university in connection with information searching, locating and using relevant information from institutional libraries and on the internet for their specific learning and educational needs. Formal and informal sources of information including electronic resources which were utilized by distance learners, the preferred format and also the barriers in seeking required information etc., are identified and examined and the factors that influence seeking information, such as gender, course of study and place of residence are analyzed in this study. It is observed from the study that there were more males i.e., 829 (57.40%) of the 1445 respondents and 616 (42.6%) were females. The results of the survey showed that 1166 (80.7%) of the respondents lived in the urban areas and 279 (19.3%) residing in the rural areas. It is found out from the study that majority of these students are occasional library users and visited the libraries more often during the contact classes. Accordingly, access to information was very much limited, public libraries had considerable impact on the achievement of such students as the results showed that 600 (41.50%) students strongly agree that public library is very much important. Internet was also used as one of the chief information sources as 1318 (91.20%) students daily used it for educational and other related activities. Distance learners’ age, educational qualification and the location of residence seem to have an influence on their information seeking behaviour given that first year undergraduate students have a tendency to start with the study materials provided by the university, while older students depend more on library than on the study materials provided by the university