Reduced Protein Model as a Tool in the Homology Modeling

Internet Electronic Conference of Molecular Design 2004, November 29 – December 12 Abstract Motivation. Theoretical prediction of protein structures is important because the number of sequenced proteins grows much faster than the number of experimentally determined 3D structures. Among theoretical methods, homology or comparative modeling of unknown 3D protein structures (targets) has been established. It is based on experimental structures of proteins (templates) with sequence similarity to the target, taking advantage of the assumption that similarity between sequences implies also structural similarity. The method is, however, limited by the degree of sequence identity. Frequently, the targettemplate sequence alignment is non-uniform along the sequence. In order to improve the method in regions of low targettemplate similarity, we have developed a reduced protein modeling approach. It allows us to generate a large number of putative conformations by energy minimization and subsequently to pre-select the most favorable conformations. The force field is based on the concept of residueresidue contact energies. Reduced structures can be translated to atomic resolution, and further evaluated.