%0 Journal Article
%T &lt;i&gt;In Silico&lt;/i&gt; Evaluation of Anti-Malarial Agents from &lt;i&gt;Hoslundia opposita&lt;/i&gt; as Inhibitors of &lt;i&gt;Plasmodium falciparum&lt;/i&gt; Lactate Dehydrogenase (P&lt;i&gt;f&lt;/i&gt;LDH) Enzyme
%A Daniel M. Shadrack
%A Stephen S. Nyandoro
%A Joan J. E. Munissi
%A Egid B. Mubofu
%J Computational Molecular Bioscience
%P 23-32
%@ 2165-3453
%D 2016
%I Scientific Research Publishing
%R 10.4236/cmb.2016.62002
%X Malaria has continued to be a health and economic problem in Africa and the world at large. Many anti-malarial drugs have been rendered ineffective due to the emergence of resistant strains of <i>Plamodium falciparum</i>. A key malaria parasite enzyme in glycolytic pathway, <i>P. falciparum</i> lactate dehydrogenase (P<i>f</i>LDH) is specially targeted for anti-malarial drugs development. Thus, the aim of this investigation was to determine the <i>in silico</i> inhibition effects of antimalarial compounds from <i>Hoslundia opposita</i> Vahl. namely hoslundin, hoslundal and hoslunddiol on P<i>f</i>LDH enzyme. The compounds were docked to the three-dimensional structure of P<i>f</i>LDH as enzyme using AutoDock Vina in PyRx virtual screening software. Binding affinity and position of the inhibitors were evaluated using PyMol software. The P<i>f</i>LDH enzyme showed two binding sites: the cofactors binding site (Site A) and secondary binding site (Site B). In the absence of the cofactor all ligands showed higher affinity than NADH, and were bound to the cofactors binding site (Site A). When docked in the presence of the cofactor, site B was the preferred binding site. Binding to cofactor site with higher binding energy than NADH suggests that these ligands could act as preferential competitive inhibitors of P<i>f</i>LDH. However, the binding to site B also suggests that they may be non-competitive allosteric inhibitors. Amino acid residues Gly99, Asn140, Phe100 and Thr97 were indicated to form hydrogen bonds with Hoslundin. Hoslunddiol showed hydrogen bonding with Thr97 and Met30, while Hoslundal formed hydrogen bond with Thr101 and Asn140.
%K P&lt
%K i&gt
%K f&lt
%K /i&gt
%K LDH
%K Hoslundin
%K Hoslundal
%K Hoslunddiol
%K Anti-Malarial
%K Docking
%U http://www.scirp.org/journal/PaperInformation.aspx?PaperID=67444