Evolutionary Algorithms in Drug Design

Designing a drug is the process of finding or creating a molecule which has a specific activity on a biological organism. Drug design is difficult since there are only few molecules that are both effective against a certain disease and exhibit other necessary physiological properties, such as absorption by the body and safety of use. The main problem of drug design is therefore how to explore the chemical space of many possible molecules to find the few suitable ones. Computational methods are increasingly being used for this purpose, among them evolutionary algorithms. This review will focus on the applications of evolutionary algorithms in drug design, in which evolutionary algorithms are used both to create new molecules and to construct methods for predicting the properties of real or yet unexisting molecules. We will also discuss the progress and problems of application of evolutionary algorithms in this field, as well as possible developments and future perspectives.     

Phytosterolaemia in three unrelated South African families

Phytosterolaemia (beta-sitosterolaemia), a rare, autosomal recessive disorder, has not hitherto been reported in Southern Africa. We report four new homozygous patients, from three unrelated families with significant beta-sitosterolaemia (6.6-11.3%), campesterolaemia (2.2-4.6%) and clearly detectable, though unquantified, levels of cholestanol. Three of the four patients had characteristic cutaneous and tendinous xanthomas within the first decade of life. The fourth patient, a 5 year old, was free of xanthomas despite persistently elevated concentrations of plant sterols in her plasma. All our patients were female bringing the male:female ratio in reported cases to 8:23. All were at or below the 50th percentile for height and weight, and presented at some stage with borderline, hypochromic anaemia associated with red cell abnormalities and thrombocytopaenia. The oldest patient showed suggestive clinical evidence of atherosclerosis affecting her aorta, ileofemoral bifurcation and possibly coronary arteries. All homozygotes responded to a diet restricted in phytosterols and the administration of cholestyramine with falls in plasma sterols of up to 68%. The recent discovery of a possible inherited defect in the synthesis of HMG CoA reductase in patients with phytosterolaemia makes this disorder a model system for studying the biological role of this enzyme in regulating the absorption and clearance of sterols other than cholesterol, and the factors governing the sterol composition of cell membranes.