Use of virtual screening, flexible docking, and molecular interaction fields to design novel HMG-CoA reductase inhibitors for the treatment of hypercholesterolemia

Dietary changes associated with drug therapy can reduce high serum cholesterol levels and dramatically decrease the risk of coronary artery disease, stroke, and overall mortality. Statins are hypolipemic drugs that are effective in the reduction of cholesterol serum levels, attenuating cholesterol synthesis in liver by competitive inhibition regarding the substrate or molecular target HMG-CoA reductase. We have herewith used computer-aided molecular design tools, i.e., flexible docking, virtual screening in large data bases, molecular interaction fields to propose novel potential HMG-CoA reductase inhibitors that are promising for the treatment of hypercholesterolemia.

Molecular dynamics, flexible docking, virtual screening, ADMET predictions, and molecular interaction field studies to design novel potential MAO-B inhibitors

Monoamine oxidase is a flavoenzyme bound to the mitochondrial outer membranes of the cells, which is responsible for the oxidative deamination of neurotransmitter and dietary amines. It has two distinct isozymic forms, designated MAO-A and MAO-B, each displaying different substrate and inhibitor specificities. They are the well-known targets for antidepressant, Parkinson`s disease, and neuroprotective drugs. Elucidation of the x-ray crystallographic structure of MAO-B has opened the way for the molecular modeling studies. In this work we have used molecular modeling, density functional theory with correlation, virtual screening, flexible docking, molecular dynamics, ADMET predictions, and molecular interaction field studies in order to design new molecules with potential higher selectivity and enzymatic inhibitory activity over MAO-B.

Dining room, Mt. Nebo House

Interior view showing fireplace and mezzanine.

Outdoor room, C House, Coorparoo, Brisbane

As seen from upper level of house.

Outdoor room, C House, Coorparoo, Brisbane

Looking towards pool deck, Hanging Basket top right.

Outdoor room, C House, Coorparoo, Brisbane

As seen from upper level of house.

Outdoor room, C House, Coorparoo, Brisbane

Looking towards Iwan from within outdoor room.

Outdoor room, Q House, Chelmer, Brisbane

View from front of property through main entrance to double-height outdoor room. Existing house on right.

Original living room, Kangaroo Point House, Kangaroo Point, Brisbane

Original living room, looking through to new outdoor room.

Original living room, Kangaroo Point House, Kangaroo Point, Brisbane

As seen from outdoor room.

Outdoor room, Kangaroo Point House, Kangaroo Point, Brisbane

Looking towards section of original house from outdoor room area. Hand-made spotted gum columns on edge of outdoor room on right.

Battened roof to outdoor room, Kangaroo Point House, Kangaroo Point, Brisbane

Timber battened concave roof and supporting structure over outdoor room area.

Outdoor room, Kangaroo Point House, Kangaroo Point, Brisbane

Dining setting, sculptures, timber columns and curved roof in outdoor room