title: Molecular modeling, in silico screening and molecular dynamics of PfPRL-PTP of P. falciparum for identification of potential anti-malarials.
abstract: Millions of deaths occur every year due to malaria. Growing resistance against existing drugs for treatment of malaria has exaggerated the problem further. There is an intense demand of identifying drug targets in malaria parasite. PfPRL-PTP protein is PRL group of phosphatase, and one of the interesting drug targets being involved in three important pathways of malaria parasite (secretion, phosphorylation, and prenylation). Therefore, in this study, we have modeled three-dimensional structure of PfPRL-PTP followed by validation of 3D structure using RAMPAGE, verify3D, and other structure validation tools. We could identify 12 potential inhibitory compounds using in silico screening of NCI library against PfPRL-PTP with Glide. The molecular dynamics simulation was also performed using GROMACS on PfPRL-PTP model alone and PfPRL-PTP-inhibitor complex. This study of identifying potential drug-like molecules would add up to the process of drug discovery against malaria parasite.
authors: a Department of Biotechnology , Central University of Rajasthan , NH-8, Bandarsindri 305801 , Rajasthan , India.
authors: Sachin
authors: S
authors: Patel
authors: a Department of Biotechnology , Central University of Rajasthan , NH-8, Bandarsindri 305801 , Rajasthan , India.
authors: Deepti
authors: D
authors: Joshi
authors: a Department of Biotechnology , Central University of Rajasthan , NH-8, Bandarsindri 305801 , Rajasthan , India.
authors: Rani
authors: R
authors: Soni
authors: a Department of Biotechnology , Central University of Rajasthan , NH-8, Bandarsindri 305801 , Rajasthan , India.
authors: Drista
authors: D
authors: Sharma
authors: a Department of Biotechnology , Central University of Rajasthan , NH-8, Bandarsindri 305801 , Rajasthan , India.
authors: Tarun Kumar
authors: TK
authors: Bhatt
mesh_terms: D000595:Amino Acid Sequence; D000962:Antimalarials / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D020134:Catalytic Domain; D003198:Computer Simulation; D055808:Drug Discovery; D008958:Models, Molecular; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D010744:Phosphoric Monoester Hydrolases / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism; D010963:Plasmodium falciparum; D011485:Protein Binding; D015800:Protozoan Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism; D015203:Reproducibility of Results; D013329:Structure-Activity Relationship
chemical_list: D000962:Antimalarials; D015800:Protozoan Proteins; D010744:Phosphoric Monoester Hydrolases
keywords: MD simulation; PRL-PTP; anti-malarials; malaria; secretory protein