title: Molecular interaction of selected phytochemicals under the charged environment of Plasmodium falciparum chloroquine resistance transporter (PfCRT) model.
abstract: Phytochemicals of Catharanthus roseus Linn. and Tylophora indica have been known for their inhibition of malarial parasite, Plasmodium falciparum in cell culture. Resistance to chloroquine (CQ), a widely used antimalarial drug, is due to the CQ resistance transporter (CRT) system. The present study deals with computational modeling of Plasmodium falciparum chloroquine resistance transporter (PfCRT) protein and development of charged environment to mimic a condition of resistance. The model of PfCRT was developed using Protein homology/analogy engine (PHYRE ver 0.2) and was validated based on the results obtained using PSI-PRED. Subsequently, molecular interactions of selected phytochemicals extracted from C. roseus Linn. and T. indica were studied using multiple-iterated genetic algorithm-based docking protocol in order to investigate the translocation of these legends across the PfCRT protein. Further, molecular dynamics studies exhibiting interaction energy estimates of these compounds within the active site of the protein showed that compounds are more selective toward PfCRT. Clusters of conformations with the free energy of binding were estimated which clearly demonstrated the potential channel and by this means the translocation across the PfCRT is anticipated.
authors.affiliation: a Department of Bioinformatics, Applied Botany Center (ABC) , University School of Sciences, Gujarat University , Ahmedabad 380009 , Gujarat , India.|b Department of Zoology, Biomedical Technology and Human Genetics , University School of Sciences, Gujarat University , Ahmedabad 380009 , India.
authors.forename: Saumya K
authors.initials: SK
authors.lastname: Patel
authors.affiliation: c Organic Chemistry Division, Combichem-Bioresource Center , National Chemical Laboratory , Pashan Road, Pune 411008 , Maharashtra , India.|d School of Health Sciences , University of KwaZulu-Natal , Durban 4000 , South Africa.
authors.forename: Vijay M
authors.initials: VM
authors.lastname: Khedkar
authors.affiliation: e School of Chemical Sciences , Central University of Gujarat , Sector-30, Gandhinagar 382030 , Gujarat , India.
authors.forename: Prakash C
authors.initials: PC
authors.lastname: Jha
authors.affiliation: a Department of Bioinformatics, Applied Botany Center (ABC) , University School of Sciences, Gujarat University , Ahmedabad 380009 , Gujarat , India.
authors.forename: Yogesh T
authors.initials: YT
authors.lastname: Jasrai
authors.affiliation: a Department of Bioinformatics, Applied Botany Center (ABC) , University School of Sciences, Gujarat University , Ahmedabad 380009 , Gujarat , India.
authors.forename: Himanshu A
authors.initials: HA
authors.lastname: Pandya
authors.affiliation: b Department of Zoology, Biomedical Technology and Human Genetics , University School of Sciences, Gujarat University , Ahmedabad 380009 , India.
authors.forename: Linz-Buoy
authors.initials: LB
authors.lastname: George
authors.affiliation: b Department of Zoology, Biomedical Technology and Human Genetics , University School of Sciences, Gujarat University , Ahmedabad 380009 , India.
authors.forename: Hyacinth N
authors.initials: HN
authors.lastname: Highland
authors.affiliation: d School of Health Sciences , University of KwaZulu-Natal , Durban 4000 , South Africa.
authors.forename: Adam A
authors.initials: AA
authors.lastname: Skelton
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry; D008024:Ligands; D026901:Membrane Transport Proteins / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D008969:Molecular Sequence Data; D064209:Phytochemicals / Q000737:chemistry* / Q000378:metabolism*; D017433:Protein Structure, Secondary; D015800:Protozoan Proteins / Q000737:chemistry* / Q000378:metabolism*; D020539:Sequence Analysis, Protein; D013237:Stereoisomerism; D040681:Structural Homology, Protein
chemical_list: D000596:Amino Acids; D008024:Ligands; D026901:Membrane Transport Proteins; C416369:PfCRT protein, Plasmodium falciparum; D064209:Phytochemicals; D015800:Protozoan Proteins
keywords: Plasmodium falciparum chloroquine; homology modeling; molecular dynamics; resistance transporter model