Current Topics in Medicinal Chemistry - Volume 16, Issue 6, 2016

All residues in an alpha helix can be characterized and dispositioned on a 2D the wenxiang diagram, which possesses the following features: (1) the relative locations of the amino acids in the α-helix can be clearly displayed regardless how long it is; (2) direction of an alphahelix can be indicated; and (3) more information regarding each of the constituent amino acid residues in an alpha helix. Owing to its intuitionism and easy visibility, wenxiang diagrams have had an immense influence on our understanding of protein structure, protein-protein interactions, and the effect of helical structural stability on protein conformational transitions. In this review, we summarize two recent applications of wenxiang diagrams incorporating NMR spectroscopy in the researches of the coiled-coil protein interactions related to the regulation of contraction or relaxation states of vascular smooth muscle cells, and the effects of α-helical stability on the protein misfolding in prion disease, in hopes that the gained valuable information through these studies can stimulate more and more widely applications of wenxiang diagrams in structural biology.

The posttranslational modification or PTM is a later but subtle step in protein biosynthesis via which to change the properties of a protein by adding a modified group to its one or more amino acid residues. PTMs are responsible for many significant biological processes, and meanwhile for many major diseases as well, such as cancer. Facing the avalanche of biological sequences generated in the post-genomic age, it is important for both basic research and drug development to timely identify the PTM sites in proteins. This Review is devoted to summarize the recent progresses in this area, with a focus on those predictors, which were developed based on the pseudo amino acid composition or PseAAC approach, and for which a publicly accessible web-server has been established. Meanwhile, the future challenge in this area has also been briefly addressed.

Protein-RNA interactions play crucial roles in numerous biological processes. However, detecting the interactions and binding sites between protein and RNA by traditional experiments is still time consuming and labor costing. Thus, it is of importance to develop bioinformatics methods for predicting protein-RNA interactions and binding sites. Accurate prediction of protein-RNA interactions and recognitions will highly benefit to decipher the interaction mechanisms between protein and RNA, as well as to improve the RNA-related protein engineering and drug design. In this work, we summarize the current bioinformatics strategies of predicting protein-RNA interactions and dissecting protein-RNA interaction mechanisms from local structure binding motifs. In particular, we focus on the feature-based machine learning methods, in which the molecular descriptors of protein and RNA are extracted and integrated as feature vectors of representing the interaction events and recognition residues. In addition, the available methods are classified and compared comprehensively. The molecular descriptors are expected to elucidate the binding mechanisms of protein-RNA interaction and reveal the functional implications from structural complementary perspective.

Aminoacyl-tRNA synthetase:transfer RNA (aaRS:tRNA) systems became recently essential targets in molecular medicine, because perturbed recognition of cognate tRNAs by aaRSs and poor precision in tRNA aminoacylation do not guarantee accurate protein biosynthesis, thus leading to diseases. Sets of identity determinants situated at particular zones of tRNA are responsible for functional accuracy. Recent work in X-ray crystallography has revealed various snapshots of aaRS:ligand complexes which represent the stages required for aminoacylation. Here we focus on a small group of class I aaRSs conserved in evolution, the ArgRSs, GluRSs, GlnRSs, and atypical LysRSs found mostly in Archaea and in a few Bacteria, that catalyze amino acid activation only in the presence of their cognate tRNAs. Structural and functional features of these aaRSs, ranked in subclass Ib, together with their peculiar mode of tRNA recognition and identity expression are reviewed and compared. Strategies to inhibit class Ib aaRS:tRNA aminoacylation systems, their dysfunction leading to human diseases, and the implications for pharmacology are outlined.

Ocular biology is a prominent area of research and advancement, as eyes are the most precious for us to see this beautiful world. Though we have overcome many ocular problems, but still challenges, no doubt exist in the path of the journey. Many ocular disorders still either have surgery or symptomatic drugs as a treatment. If we could get a better preventive way or single drug with many and more potential effects, will definitely be a boon for our society. Keeping the way we tried to focus on the impending effects of phytochemicals on some important ocular disorders. Our study promised with virtual screening based on important insilico protocols that can be a landmark for better futuristic approach towards novel drug development. As a selection Eales’ Disease, Diabetic Retinopathy, Uveitis, Age related Macular Disorder, CRVO were taken. Causative Protein identification is the basic of study and further advance Insilico approaches were based on this target in respective disorders. Retinol Binding protein-3 and Retinal S antigen protein in case of Eales, Erythropoietin in the case of Diabetic Retinopathy, Nucleotide-binding oligomerization domain-containing protein-2 in case of Uveitis, Hemicentin-1 in case of Age related Macular Disorder, Coagulation Factor-V in case of CRVO were identified. Insilico characterization, Secondary and Tertiary structure prediction makes the study more prominent towards virtual screening. Virtual Screening was based on the parameters of docking, which reflects the potentiality of Ginkgolide, D-pinitol, Gugglesterones, Berberine and Curcumin herbal molecules against above mentioned ocular disorders respectively. Study signifies about the spectacular vision of herbal uses just to limit the vast side effects of synthetic chemicals used as ocular drugs.

Schizophrenia is a severe complex disabling disease that has impaired about 1% of the total population. It is widely recognized that schizophrenia is caused by the abnormal immune system. However, the current genome-wide association study (GWAS) of schizophrenia did not identify any cytokine molecules except genes in the major histocompatibility complex (MHC) region, suggesting that new strategies are needed to find out the effects of cytokines during the development of Schizophrenia. Recently, increasing evidences have found the comorbidity of schizophrenia with tuberculosis. To narrow down the scope of cytokines and reveal the core culprit, we first systematically review the common cytokines between these two diseases, followed by summarizing the core cytokines' interaction and modulation. The findings thus obtained may provide useful insights into the pathogeneses of both schizophrenia and tuberculosis from the angle of cytokines.

Blood coagulation is healthy and lifesaving because it can stop bleeding. It can, however, be a troublemaker as well, causing serious medical problems including heart attack and stroke. Body has complex blood coagulation cascade to modulate the blood clots. In the environment of plasma, the blood coagulation cascade is regulated by antithrombin, which is deemed one of the most important serine protease inhibitors. It inhibits thrombin; it can inhibit factors IXa and Xa as well. Interestingly, its inhibitory ability will be significantly increased with the existence of heparin. In this minireview paper, we are to summarize the structural features of antithrombin, as well as its heparin binding modes and anti-coagulation mechanisms, in hopes that the discussion and analysis presented in this paper can stimulate new strategies to find more effective approaches or compounds to modulate the antithrombin.