Edited by Gunnar von Heijne Abstract Cellular metabolism is a molecular economy that is functionally organised into supply and demand blocks linked by metabolic products and cofactor cycles. Supply^demand analysis allows the behaviour, control and regulation of metabolism as a whole

mitochondrial Oxa1p, is a component of the Sec translocase Koch et al., 1999), although the exact subset of innerPier A.Scotti, Malene L.Urbanus, membrane proteins that depends on the SRP has yet toJosef Brunner1, Jan-Willem L.de Gier2, be defined.Gunnar von Heijne2, Chris van der Does3

signal peptide prediction accuracy by simulated neural network I.Ladunga1, F.Czakd2, I.Csabai2 and T.Geszti2 The accuracy of distinguishing amino-terminal signal peptides from cytosolic proteins has been improved to 95 % by combining a neural network classifier with von Heijne's statistical

the signal peptide by considering a minimum number of predicted TM segments for further analysis (Wallin and von Heijne, 1998), while another treated the signal peptide directly by removing it first from the query sequence

for chloroplasts are enriched in both hydroxylated and hydrophobic amino acids and are devoid of acidic resi-dues (Von Heijne et al. 1989). However, these targeting se-quences are surprisingly variable in amino acid sequence and overall amino acid composition and range in length

in sequenced genomes (Boyd et al., 1998; Wallin & von Heijne, 1998). New approaches, such as the one presented here, are being developed to identify reversible steps in membrane protein folding pathways and to measure how they are thermodynamically coupled to environmental properties (Booth et al., 1997

and the orientation of TMS to the me brane lipid bilayer. For this reason, high performx.K prediction mpre ds of TM topologyfrom amm acid sequence are becom9K increasingly needed. Many of TM topology predictionmred ds have been proposed already such as KKD [Klein, P. et al., 1985], TopPred 2 [Claros, M. G. and von

(von Heijne, 1986) or neuronal network algorithms using a 20-letter amino acid code (Nielsen et al., 1997). In this work, the feasibility of using physicochemical characteristics of amino acids for recognizing cleavage sites in signal peptides is studied. The algorithm AddDel (Zagoruiko, 1999

). These signal sequences are of widely differing primary structure with an overall hydrophobic nature being the only common feature (von Heijne, 1988). The way in which such widely diverse signals are recognized is poorly understood although it is central to the way in which such signals function. Eukaryotic

'knobs-into-holes' geometries. Fold space The abstract space of all protein folds. 'Knobs-into-holes' geometry The classic mode of helix-helix packing in which side-chains on one helix fit into spaces between side chains on the opposite helix. Membrane-protein topology Gunnar von