Protein-ligand interaction studies and identification of new drug-like hits as cannabinoid receptor modulators

The cannabinoid receptors (CB1 and CB2) belong to the family of class A GPCRs. The CB1 receptor is predominately found in the central nervous system and regulates various neuromodulatory and physiological processes while CB2 receptors are found in peripheral tissues, particularly in the immune system tissues. This dissertation reports several projects including: (1) an examination of the putative binding modes of Cannabis-derived ligands with CB1 and CB2 receptors, (2) the identification of novel CB1 inverse agonists, and (3) the identification of allosteric site(s) in the CB2 receptor and screening of new CB2 allosteric modulators (AMs). Chapter 1 describes background information on cannabinoids and the endocannabinoid system. Chapter 2 focuses on the structure-activity relationships of Cannabis-derived ligands with CB1 and CB2 receptors. These compounds are known to exhibit nanomolar to micromolar affinities against the CB1 and CB2 receptors; however, little-to-no information is available about how they interact with the receptors at the molecular level. To understand the putative binding interactions of these ligands with the CB receptors, molecular docking and binding free-energy calculations were performed. The modeling results agree well with the experimental results and delineate key residues of CB1 and CB2 receptors that are engaged in H-bonding, aromatic stacking, and hydrophobic interactions with the ligand. Chapter 3 focuses on the identification of new CB1 inverse agonists using protein structure-based virtual screening. These compounds exhibited nanomolar to micromolar binding affinities against the CB1 receptor and antagonized basal GTPγS functional activity consistent with inverse agonist behavior. These compounds represent novel scaffolds that could be used to develop new CB1 inverse agonists with fewer or null psychiatric side effects compared to rimonabant. Chapter 4 focuses on the identification and characterization of CB2 allosteric site(s). Using known CB2 negative AMs, the binding energy of representative complexes after molecular dynamics studies validated the binding poses of AMs. Virtual screening revealed seven potential AMs and they have been submitted for in vitro testing. The results from this study could lead to the discovery of more effective and selective CB2 AMs. Finally, Chapter 5 includes the summary and conclusions of the research presented in this dissertation

EFFECT OF CORE IMMOVABILITY TRAINING ON TRUNK STABILITY OF CRICKET PLAYERS

Core strength is the base of all physical activity. Core strength plays vast role for development of overall skill. Purpose: The prevalent objectives of the study were to find out the effect of core stability training on strength of university level cricket players. Approach: Fifty (50) university level cricket players from Delhi/ NCR were selected as the subjects for this study whose age were ranging between 18-21 yrs. These subjects were randomly divided into two equal groups (control and experimental group) based on the scores obtained from vertical jump test. A systematic core immovability training for 8 weeks (five days per week) was given to the experimental group. The control group received no treatment. Pre-test and post-test data were collected on leg strength and back strength for both the groups. The data were further analysed by using one way ANOVA to find out the training effects if any on the subjects. Result: The result of the study showed that there was significant improvement on back and leg strength of the experimental group. Conclusion: It was concluded that core training useful in improving the strength ability of the cricket players.  Article visualizations

Review of Reconfigurable Microstrip Patch antenna for Wireless Application

In recent time, world have seen a rapid growth in wireless communication. Development in antenna from single band to dual band and multi band had made the antenna system more compact. A frequency reconfigurable microstrip antenna using a PIN diode for multiband operation is using many application and hot research area. In this paper, reconfigurable microstrip patch antennas and their types like frequency, polarization, radiation pattern and gain are described

SOME RESULTS ON RICCI SOLITON ON CONTACT METRIC MANIFOLDS

The objective of this paper is to study the nature of Ricci soliton admitting various type of contact metric manifolds such as Kenmostu manifold, LP Sasakian manifold and LCS manifold. In this paper, it is proved that a Kemnotsu Ricci soliton is expanding, whereas the LP-Sasakian Ricci soliton is shrinking. Further, the conditions have been obtained on $(LCS)_{n}$ Ricci soliton to be expanding, shrinking and steady and the results are verified by suitable examples. It is also proved that the possible values of soliton constant is the set of all even integers \ZZ^{2n} and the set of negative integres \ZZ^{-} respectively for Kenmostu Ricci soliton and LP Sasakian Ricci Soliton and if the (LCS) Ricci soliton is expanding then soliton constant lies on the interval $(0, \infty)$ and for shrinking it lies on $(-\infty, 0)$. The Projectively flat cases for the above manifolds are also discussed to be expanding, shrinking and steady. Finally, we study these Ricci solitons admitting Ricci semi-symmetric condition $R.S=0$ and prove that the soliton constant $\lambda$ is an eigen value of metric tensor $g$ with respect to associated vector field $\xi$