Design of inhibitors for nucleoside hydrolase from Leishmania donovani using molecular dynamics studies

Journal of the Brazilian Chemical Society

França, Tanos C. C.¹  Instituto Militar de Engenharia, Rio de Janeiro, Brazil¹  Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil¹  Tinoco, Luzineide W.¹  Reboredo, Bruno M.¹  Figueroa-Villar, José D.¹  Rennó, Magdalena N.¹  Rocha, Maria do Ramo M.¹ 

关键词: visceral leishmaniasis;    Leishmania donovani;    metalloproteins;    homology modeling;    molecular dynamics;   

DOI  :  10.1590/S0103-50532008000100011

学科分类：化学（综合）

来源: SciELO

【 摘 要 】

In this work we propose the first homology model for nucleoside hydrolase from Leishmania donovani, built based on the crystallographic structures of Crithidia fasciculata and Leishmania major nucleoside hydrolases. We used the interaction information from the crystallographic model of the enzyme of C. fasciculata in complex with the inhibitor p-aminophenyliminoribitol, to design two new potential inhibitors, which present new interactions with some residues of the hydrophobic pocket of the model active site. Molecular dynamics simulations of the prototypes inside the active sites of the model and the template enzymes showed that, differently from p-aminophenyliminoribitol, they remained tightly bound inside the active sites, interacting strongly with the amino acids from the hydrophobic pocket.

【 授权许可】

Unknown