Molecular dynamic modeling of CYP51B in complex with azole inhibitors.

Cytochrome P450 14α-sterol demethylase (CYP51), the key enzyme in sterol biosynthesis pathway, is an important target protein of cholesterol-lowering agents, antifungal drugs, and herbicides. CYP51B enzyme is one of the CYP51 family members. In the present study, we have chosen four representative inhibitors of CYP51B: diniconazole (Din), fluconazole (Flu), tebuconazole (Teb), and voriconazole (Vor), and launched to investigate the binding features of CYP51B-inhibitor and gating characteristics via molecular docking and molecular dynamics (MD) simulations.

Molecular dynamics investigations of membrane-bound CYP2C19 polymorphisms reveal distinct mechanisms for peripheral variants by long-range effects on the enzymatic activity.

Increasing sophistication in methods used to account for human polymorphisms in susceptibility to drug metabolism has been one of the success stories in the prevention of adverse drug reactions. Genetic polymorphisms in drug-metabolizing enzymes can affect enzyme activity and cause differences in treatment response or drug toxicity. CYP2C19 is one of the most highly polymorphic CYP enzymes and acts on 10-15% of drugs in current clinical use.

Dissecting genetic networks underlying complex phenotypes: the theoretical framework.

Great progress has been made in genetic dissection of quantitative trait variation during the past two decades, but many studies still reveal only a small fraction of quantitative trait loci (QTLs), and epistasis remains elusive. We integrate contemporary knowledge of signal transduction pathways with principles of quantitative and population genetics to characterize genetic networks underlying complex traits, using a model founded upon one-way functional dependency of downstream genes on upstream regulators (the principle of hierarchy) and mutual functional dependency among related genes (functional genetic units, FGU). Both simulated and real data suggest that complementary epistasis contributes greatly to quantitative trait variation, and obscures the phenotypic effects of many 'downstream' loci in pathways.

[Identification of markers linked to resistance locus of Marssonina leaf spot in poplars by bulked segregant analysis(BSA)].

DNA markers linked to resistance locus of Marssonina leaf spot in poplars were found by bulked segregant analysis(BSA). The bulks consisted of individual with a extreme phenotype taken from a population of 91 F1 clones,which is a progeny of Populus deltoides Bartr.cv.