RESUMO
Thirty-nine wheat genotypes were studied to estimate their partial resistance levels to leaf rust at Behira governortae during three growing seasons, i.e. 2016/2017, 2017/2018 and 2018/2019. In these genotypes, partial resistance was characterized using final leaf rust severity (FRS %) and area under disease progress curve (AUDPC). Of the tested genotypes, only three wheat varieties; Giza 171, Misr 3 and Sohag 5 showed complete resistance. Further, 28 of the 39 genotypes had partial resistance as they revealed low and/or moderate values of FRS (%) and AUDPC (not exceeding 30% and 300, respectively). The other eight varieties were fast rusting, as they displayed the maximum values of FRS (%) and AUDPC. The four monogenic lines; Lr 34, Lr 46, Lr 67 and Lr 68 were identified in the wheat varieties using linked molecular markers; csLV34, Xgwm259, CFD71 and csGSR. Phenotypic results of the wheat varieties were confirmed by molecular marker analysis.
Assuntos
Basidiomycota , Resistência à Doença/genética , Doenças das Plantas/genética , Triticum/genética , Basidiomycota/genética , Mapeamento Cromossômico , Genes de Plantas , Estudos de Associação Genética , Marcadores Genéticos , Genótipo , Fenótipo , Doenças das Plantas/microbiologiaRESUMO
Molecular dynamics simulations and binding free energy calculations were used to provide an understanding of the impact of active site drug-resistant mutations of the South African HIV protease subtype C (C-SA HIV PR), V82A and V82F/I84V on drug resistance. Unique per-residue interaction energy 'footprints' were developed to map the overall drug-binding profiles for the wild type and mutants. Results confirmed that these mutations altered the overall binding landscape of the amino acid residues not only in the active site region but also in the flaps as well. Four FDA-approved drugs were investigated in this study; these include ritonavir (RTV), saquinavir (SQV), indinavir (IDV), and nelfinavir (NFV). Computational results compared against experimental findings were found to be complementary. Against the V82F/I84V variant, saquinavir, indinavir, and nelfinavir lose remarkable entropic contributions relative to both wild-type and V82A C-SA HIV PRs. The per-residue energy 'footprints' and the analysis of ligand-receptor interactions for the drug complexes with the wild type and mutants have also highlighted the nature of drug interactions. The data presented in this study will prove useful in the design of more potent inhibitors effective against drug-resistant HIV strains.
Assuntos
Farmacorresistência Viral/efeitos dos fármacos , Protease de HIV/genética , Protease de HIV/metabolismo , Simulação de Dinâmica Molecular , Mutação , África , Domínio Catalítico , Inibidores da Protease de HIV/química , Inibidores da Protease de HIV/farmacologia , Estrutura Molecular , TermodinâmicaRESUMO
We report the first account of a comparative analysis of the binding affinities of nine FDA-approved drugs against subtype B as well as the South African subtype C HIV PR (C-SA). A standardized protocol was used to generate the inhibitor/C-SA PR complexes with the relative positions of the inhibitors taken from the corresponding X-ray structures for subtype B complexes. The dynamics and stability of these complexes were investigated using molecular dynamics calculations. Average relative binding free energies for these inhibitors were calculated from the molecular dynamics simulation using the molecular mechanics generalized Born surface area method. The calculated energies followed a similar trend to the reported experimental binding free energies. Postdynamic hydrogen bonding and electrostatic interaction analysis of the inhibitors with both subtypes reveal similar interactions. Most inhibitors show slightly weaker binding affinities for C-SA PR. Molecular dynamics studies demonstrated increased flap movement for C-SA PR, which can perhaps explain the weaker affinities. This study serves as a standardized platform for optimizing the design of future more potent HIV C-SA PR inhibitors.