Optimised amino acid specific weighting factors for unbound protein docking

For up to 86% of the evaluated complexes a near-native structure was within the top 5% of the ranked prediction output. The weighting factors obtained by the optimisation procedure correlate to a certain extent with the flexibility of the amino acids, their hydrophobicity and with their propensity to be in the interface.Use of the optimised amino acid specific parameters yields a strong increase of near-native structures on the first ranks of the prediction.Protein-protein interactions and complex formation play a central role in a broad range of biological processes, including hormone-receptor binding, protease inhibition, antibody-antigen interaction and signal transduction [1]. As structural genomics projects proceed, we are confronted with an increasing number of structurally known proteins that are functionally uncharacterised. To identify how two proteins are interacting will be particularly important for elucidating functions and designing inhibitors[2]. Although predicting around 50 percent false positive interactions [3], high throughput interaction discovery methods, such as the yeast two hybrid system, suggest thousands of protein-protein interactions and therefore also imply that a large fraction of all proteins interact with other proteins [4].Since many biological interactions occur in transient complexes whose structures often cannot be determined experimentally, it is important to develop computational docking methods which can predict the structure of complexes with a proper accuracy [5].Docking algorithms are developed to predict in which orientation two proteins are likely to bind under natural conditions. They can be split in a sampling step followed by a scoring step. A collection of putative structural complexes is generated by scanning the full conformational space in the first step. Afterwards the putative complexes are ranked according to scoring functions based on geometrical and chemical complementarity.For the scanning of the conformation