Relibase is a database system that has been specially designed to handle protein-ligand data. Included within Relibase is a tool that can be used to systematically analyse protein-ligand interaction patterns specified by three-dimensional (3D) constraints, revealing favorable combinations of interacting functional groups and their preferred interaction geometries. This paper describes the Relibase 3D query tools, including novel extensions (Relibase+) for handling crystallographic packing effects. Examples illustrating the broad range of functionality for defining 3D interaction patterns and the application of such queries in drug design comprise carbonyl-carbonyl interactions, zinc binding site environments, and ligand-ligand interactions in the crystal packing.

Binding Sites↗

PubMedDate not supplied

Effects of hypoxia, simulated ischemia and reoxygenation on the contractile function of human atrial trabeculae.

Hypoxia, ischemia and reoxygenation cause contractile dysfunction which will be characterized by the time course of isometric contraction of human atrial trabeculae. Post-rest potentiation (PRP) and postextrastimulatory potentiation (PEP) were elicited to obtain indirect information about the the role of the sarcoplasmic reticulum (SR) in excitation-contraction coupling. As lipid peroxidation could cause SR dysfunction, thiobarbituric acid reactive substances (TBARS) were measured. After 30 min of hypoxia (H) or simulated ischemia (H combined with acidosis-SI), contractile force decreased to 15% and 6%, respectively, of control (p < or = 0.05), whereas the normalized rate of both contraction and relaxation increased. In group H, rapid reoxygenation produced a recovery of contractile force to about 60%. After post-hypoxic reoxygenation the TBARS concentration was increased. In group SI, rapid reoxygenation and a rather gradual correction of acidosis produced complete recovery of contractile force. PRP and PEP were maintained during H and SI. Particularly post-ischemic reoxygenation caused a marked depression of PRP and partly of PEP. Thus, alteration of SR Ca2+ handling occurs predominantly during reoxygenation rather than during H or SI, probably associated with the damaging effect of increased oxygen radicals. The depression of potentiation occurred along with delayed relaxation, temporary increased resting force, mechanical alternans, and spontaneous activity which are further characteristics for SR dysfunction. Thus, for a possibly beneficial effect of low pH during SI combined with its gradual correction during reoxygenation on the recovery of contractile function, developed force should not be the only index.

Action Potentials↗