In most of the pathogenic organisms including Plasmodium falciparum, isoprenoids are synthesized via MEP (MethylErythritol 4-Phosphate) pathway. LytB is the last enzyme of this pathway which catalyzes the conversion of (E)-4-hydroxy-3-methylbut-2-en-1-yl diphosphate (HMBPP) into the two isoprenoid precursors: isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP). Since the MEP pathway is not used by humans, it represents an attractive target for the development of new antimalarial compounds or inhibitors. Here a systematic in-silico study has been conducted to get an insight into the structure of Plasmodium lytB as well as its affinities towards different inhibitors. We used comparative modeling technique to predict the three dimensional (3D) structure of Plasmodium LytB taking E. Coli LytB protein (PDB ID: 3KE8) as template and the model was subsequently refined through molecular dynamics (MD) simulation. A large ligand dataset containing diphospate group was subjected for virtual screening against the target using GOLD 5.2 program. Considering the mode of binding and affinities, 17 leads were selected on basis of binding energies in comparison to its substrate HMBPP (Gold.Chemscore.DG:-20.9734 kcal/mol). Among them, 5 were discarded because of their inhibitory activity towards other human enzymes. The rest 12 potential leads carry all the properties of any "drug like" molecule and the knowledge of Plasmodium LytB inhibitory mechanism which can provide valuable support for the antimalarial inhibitor design in future.. Structural model of the Plasmodium falciparum Thioredoxin reductase: a novel target for antimalarial drugs. Journal of vector borne diseases, 46: 171-83. Retrieved from http://www.mrcindia.org/, [3] Berendsen, H.

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It is well known that proteins denature under high pressure. The mechanism that underlies such a process is still not clearly understood, however, giving way to controversial interpretations. Using molecular dynamics simulation on systems that may be regarded experimentally as limiting examples of the effect of high pressure on globular proteins, such as lysozyme and apomyoglobin, we have effectively reproduced such similarities and differences in behavior as are interpreted from experiment. From the analysis of such data, we explain the experimental evidence at hand through the effect of pressure on the change of water structure, and hence the weakening of the hydrophobic effect that is known to be the main driving force in protein folding.