A model for the C5a receptor and for T its interaction with the ligand

A model of the C5a receptor was built based on the assumptionthat the seven membrane-spanning helices of known inward/outwarddirection are in an arrangement roughly similar to that in bacteriorhodopsin.Guidelines for the positioning of the helices were cysteinepairing, ‘ridges into grooves’ interdigitation ofside chains and aromatic cluster formation. The chain segmentsprotruding from the membrane are too short for folding intoan independent ectodomain. The only longer segment (179–202)is tied down in its centre onto the membrane by a disulphidebridge and, thereby, made into two short loops as well. Ideasof the interaction of the C5a receptor with its ligand werederived mainly from the search for accommodation of the functionallyessential arginine residues 40 and 74 of C5a. Asp82 is the onlycharged residue in a pocket {small tilde}20 A below the receptorsurface and is conserved in the rhodopsin superfamily. It commendsitself for binding Arg74 which is the tip of the flexible C-terminalchain of C5a, and rules out Arg40 in the structurally well-definedpart of the molecule. The latter may bind to Glul80 at the bottomof a more shallow pocket which happens to resemble the substrate-bindingsite of trypsin.     

Search algorithms for automated validation

A novel search technique called highway search is introduced. The search technique relies on a highway simulation which takes several homogeneous walks through a (possibly infinite) state space. Furthermore, we provide a memory-efficient algorithm that approximates a highway search and we prove that, under particular conditions, they coincide. The effectiveness of highway search is compared to two mainstream search techniques, viz. random search and randomised depth-first search. Our results demonstrate that randomised depth-first search explores the least amount of states in the effort of finding states of interest, whereas a highways search yields the shortest witnessing traces to such states.