174 research outputs found
Utility of apremilast in the treatment of psoriasis
Psoriasis is an autoimmune disease that affects more than one bodily system with predominantly skin and also joint manifestations affecting almost 2% of the world population that occurs primarily due to immune dysregulation. Apremilast is an oral, selective inhibitor of phosphodiesterase-4 (PDE4) enzymes. Inhibition of PDE-4 results in specific elevation of cAMP, an innately occurring intracellular secondary messenger that functions as a modulator of inflammatory responses. The drug is taken orally in strengths of 10, 20 and 30 mg. The drug may be a suitable alternative to different systemic therapies. Apremilast is a much-needed molecule for the treatment of psoriasis that is resistant to first line therapy and also useful in combination therapies
The AC/AG Diplotype for the 118A>G and IVS2Β +Β 691G>C Polymorphisms of OPRM1 Gene is Associated with Sleep Quality Among Opioid-Dependent Patients on Methadone Maintenance Therapy
Induced Fit or Conformational Selection? The Role of the Semi-closed State in the Maltose Binding Protein
Distinguishing Binders from False Positives by Free Energy Calculations: Fragment Screening Against the Flap Site of HIV Protease
Molecular docking is a powerful tool used in drug discovery and structural biology for predicting the structures of ligandβreceptor complexes. However, the accuracy of docking calculations can be limited by factors such as the neglect of protein reorganization in the scoring function; as a result, ligand screening can produce a high rate of false positive hits. Although absolute binding free energy methods still have difficulty in accurately rank-ordering binders, we believe that they can be fruitfully employed to distinguish binders from nonbinders and reduce the false positive rate. Here we study a set of ligands that dock favorably to a newly discovered, potentially allosteric site on the flap of HIV-1 protease. Fragment binding to this site stabilizes a closed form of protease, which could be exploited for the design of allosteric inhibitors. Twenty-three top-ranked proteinβligand complexes from AutoDock were subject to the free energy screening using two methods, the recently developed binding energy analysis method (BEDAM) and the standard double decoupling method (DDM). Free energy calculations correctly identified most of the false positives (β₯83%) and recovered all the confirmed binders. The results show a gap averaging β₯3.7 kcal/mol, separating the binders and the false positives. We present a formula that decomposes the binding free energy into contributions from the receptor conformational macrostates, which provides insights into the roles of different binding modes. Our binding free energy component analysis further suggests that improving the treatment for the desolvation penalty associated with the unfulfilled polar groups could reduce the rate of false positive hits in docking. The current study demonstrates that the combination of docking with free energy methods can be very useful for more accurate ligand screening against valuable drug targets
Modular protein-RNA interactions regulating mRNA metabolism: a role for NMR
Here we review the role played by transient interactions between multi-functional proteins and their RNA targets in the regulation of mRNA metabolism, and we describe the important function of NMR spectroscopy in the study of these systems. We place emphasis on a general approach for the study of different features of modular multi-domain recognition that uses well-established NMR techniques and that has provided important advances in the general understanding of post-transcriptional regulation
The Opposing Roles of IVS2+691 CC Genotype and AC/AG Diplotype of 118A>G and IVS2+691G>C of OPRM1 Polymorphisms in Cold Pain Tolerance Among Opioid-Dependent Malay Males on Methadone Therapy
Mesoflowers: A new class of highly efficient surface-enhanced Raman active and infrared-absorbing materials
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