Disassociation of β1-α1-β2 from the α2-α3 domain of prion protein (PrP) is a prerequisite for the conformational conversion of PrP into PrP: Driven by the free energy landscape.

Misfolding of the cellular prion protein (PrP) into β-sheet-rich scrapie form (PrP) is associated with transmissible spongiform encephalopathies. A point mutation F198S is responsible for the development of a rare inherited Gerstmann-Straussler-Scheinker disease caused by the aggregation of PrP. Thus, identification and the structural characterization of aggregation-prone regions are essential to delineate the conversion of PrP to the disease-associated PrP upon F198S mutation.

Glaucoma Pred: Glaucoma prediction based on Myocilin genotype and phenotype information.

Glaucoma is the second leading cause of blindness after cataract and is heterogeneous in nature. Employing a genetic approach for the detection of the diseased condition provides an advantage that the gene responsible for the disease can be identified by genetic test. The availability of predictive tests based on the published literature would provide a mechanism for early detection and treatment.

Discovery of pyridyl-based inhibitors of -myristoyltransferase.

-Myristoyltransferase (NMT) represents an attractive drug target in parasitic infections such as malaria due to its genetic essentiality and amenability to inhibition by drug-like small molecules. Scaffold simplification from previously reported inhibitors containing bicyclic cores identified phenyl derivative , providing a versatile platform to study the effects of substitution on the scaffold, which yielded pyridyl . This molecule exhibited improved enzyme and cellular potency, and reduced lipophilicity compared to inhibitor .

Design and synthesis of high affinity inhibitors of Plasmodium falciparum and Plasmodium vivax N-myristoyltransferases directed by ligand efficiency dependent lipophilicity (LELP).

N-Myristoyltransferase (NMT) is an essential eukaryotic enzyme and an attractive drug target in parasitic infections such as malaria. We have previously reported that 2-(3-(piperidin-4-yloxy)benzo[b]thiophen-2-yl)-5-((1,3,5-trimethyl-1H-pyrazol-4-yl)methyl)-1,3,4-oxadiazole (34c) is a high affinity inhibitor of both Plasmodium falciparum and P. vivax NMT and displays activity in vivo against a rodent malaria model.

Validation of N-myristoyltransferase as an antimalarial drug target using an integrated chemical biology approach.

Malaria is an infectious disease caused by parasites of the genus Plasmodium, which leads to approximately one million deaths per annum worldwide. Chemical validation of new antimalarial targets is urgently required in view of rising resistance to current drugs. One such putative target is the enzyme N-myristoyltransferase, which catalyses the attachment of the fatty acid myristate to protein substrates (N-myristoylation).