In silico 3-D structure prediction and molecular docking studies of inosine monophosphate dehydrogenase from Plasmodium falciparum.
Comput Biol Chem
; 71: 10-19, 2017 Dec.
Article
en En
| MEDLINE
| ID: mdl-28957725
ABSTRACT
Growing resistance in malarial parasites, particularly in Plasmodium falciparum needs a serious search for the discovery of novel drug targets. Inosine monophosphate dehydrogenase (IMPDH) is an important target for antimalarial drug discovery process in P. falciparum for the treatment of malaria. In the absence of x-ray crystal structure of this enzyme, homology modeling proved to be a reasonable alternate to study substrate binding mechanisms of this enzyme. In this study, a 3-D homology model for P. falciparum IMPDH was constructed taking human IMPDH (PDB code 1NF7) as template. Furthermore, an in-silico combinatorial library of ribavirin (RVP) derivatives (1347 molecules) was designed and virtually screened for ligands having selectively greater binding affinity with Plasmodium falciparum IMPDH relative to human IMPDH II. A total of five Ribavirin derivatives were identified as having greater binding affinity (-126 to -108Kcal/mol and -9.4 to -8.6Kcal/mol) with Plasmodium falciparum IMPDH. These five inhibitors should be used as selective and potent for Plasmodium falciparum IMPDH. Such type of study will provide information to synthetic medicinal chemist to enhance the potential of compounds (RVP derivatives) as chemotherapeutic agents to fight against the increasing burden of malarial infections.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Plasmodium falciparum
/
Simulación por Computador
/
Simulación del Acoplamiento Molecular
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IMP Deshidrogenasa
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Idioma:
En
Revista:
Comput Biol Chem
Asunto de la revista:
BIOLOGIA
/
INFORMATICA MEDICA
/
QUIMICA
Año:
2017
Tipo del documento:
Article
País de afiliación:
China