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We conclude with a discussion of the most pressing technological and regulatory limitations in current practice, and how these could be addressed by future research.Kynurenine 3-monooxygenase (KMO) regulates the levels of bioactive substances in the kynurenine pathway of tryptophan catabolism and its activity is tied to so many diseases that finding an appropriate inhibitor for KMO has become an urgent task. This especially proved to be difficult for the central nervous system related diseases due to the requirement that the supposed inhibitor should be both blood brain barrier permeable and should not cause hydrogen peroxide as a harmful side product. In this in silico study, we present our step-wise approach, whose starting point is based on the important experimental observations. To tackle the problem, a library of 7561938 structures was obtained from Zinc15 database utilizing the tranche browser. From this library, a subset of 501777 structures was determined with the considerations of their functional groups that constrain their applicability. Then, the binding affinity ranking of this set of structures was determined via virtual screening. Starting from the structures whose affinities are the highest among this subset, the ADMET properties were checked through in silico methods and the binding properties of the selected inhibitor candidates were further investigated via molecular dynamics simulations and MM/GBSA calculations. According to the computational results of this study, ZINC_71915355 has passed all the evaluations and is a potentially BBB permeable structure that can inhibit KMO. Additionally, ZINC_19827377 was identified as a new potential KMO inhibitor which may be more suitable for peripheral administration. From the in silico study presented herein, ZINC_71915355 and ZINC_19827377 structures, which showed high binding affinity without harmful H2O2 production, along with the tailored properties can now serve as powerful candidates for KMO inhibition and these hits are worth of further experimental validation.DNA sequence similarity analysis is an essential task in computational biology and bioinformatics. In nearly all research that explores evolutionary relationships, gene function analysis, protein structure prediction and sequence retrieving, it is necessary to perform similarity calculations. As an alternative to alignment-based sequence comparison methods, which result in high computational cost, alignment-free methods have emerged that calculate similarity by digitizing the sequence in a different space. In this paper, we proposed an alignment-free DNA sequence similarity analysis method based on top-k n-gram matches, with the prediction that common repeating DNA subsections indicate high similarity between DNA sequences. In our method, we determined DNA sequence similarities by measuring similarity among feature vectors created according to top-k n-gram match-up scores without the use of similarity functions. We applied the similarity calculation for three different DNA data sets of different lengths. The phylogenetic relationships revealed by our method show that our trees coincide almost completely with the results of the MEGA software, which is based on sequence alignment. Our findings show that a certain number of frequently recurring common sequence patterns have the power to characterize DNA sequences.Cytochrome P450 oxidoreductase (POR) is a steroidogenic and drug-metabolizing enzyme. selleck chemical It helps in the NADPH dependent transfer of electrons to cytochrome P450 (CYP) enzymes for their biological activity. In this study, we employed integrative computational approaches to decipher the impact of proline to leucine missense mutation at position 384 (P384L) in the connecting/hinge domain region which is essential for the catalytic activity of POR. Analysis of protein stability using DUET, MUpro, CUPSAT, I-Mutant2.0, iStable and SAAFEC servers predicted that mutation might alter the structural stability of POR. The significant conformational changes induced by the mutation to the POR structure were analyzed by long-range molecular dynamics simulation. The results revealed that missense mutation decreased the conformational stability of POR as compared to wild type (WT). The PCA based FEL analysis described the mutant-specific conformational alterations and dominant motions essential for the biological activity of POR. The LIGPLOT interaction analysis showed the different binding architecture of FMN, FAD, and NADPH as a result of mutation. The increased number of hydrogen bonds in the FEL conformation of WT proved the strong binding of cofactors in the binding pocket as compared to the mutant. The porcupine plot analysis associated with cross-correlation analysis depicted the high-intensity flexible motion exhibited by functionally important FAD and NADPH binding domain regions. The computational findings unravel the impact of mutation at the structural level, which could be helpful in understanding the molecular mechanism of drug metabolism.Restless legs syndrome (RLS) affects one in five pregnant women. This review aims to synthesise evidence regarding gestational RLS and its consequences on pregnant women and neonates. Search of Embase, MEDLINE, PsycINFO, Maternity and Infant Care and Scopus was conducted in July 2018 using MeSH headings and keywords for 'restless legs syndrome' and 'pregnancy' or 'birth'. Our search identified 16 eligible studies from 12 countries published between 2004 and 2018 concerning gestational RLS and one or more maternal, delivery or neonatal outcomes. The most consistent associations were observed between gestational RLS and increased risks of gestational hypertension, pre-eclampsia, and peripartum depression. There were mixed findings for caesarean delivery, preterm birth and low birth weight, with the majority reporting no association with gestational RLS. Gestational RLS was not associated with postpartum haemorrhage, gestational diabetes, fetal distress, or low Apgar scores. Future research is needed to investigate whether effective treatment of RLS can mitigate these potential harms. Validated methods for diagnosing RLS in pregnancy would support research in this growing field.