Modeling of Biomolecular Systems Interactions, Dynamics, and Allostery: Bridging Experiments and Computations - September 10-14, 2014, Istanbul, Turkey

Modeling of Biomolecular Systems Interactions, Dynamics, and Allostery Poster Session II

48-POS Board 1 Similarity-based 3D Modeling of Compound -Protein Complexes Takeshi Kawabata , Akira Kinjo, Haruki Nakamura. Osaka University, Suita, Osaka, Japan.

3D complex structures of proteins and other molecules provide a clue for mechanism of interaction. It is important to model them in computational methods because only small amount of 3D complex structures for known interacting molecular pairs are available. Similarity-based modeling (template-based modeling) of compound-protein complexes can be performed by similar way to model protein monomers. If the experimental complex 3D data of a similar compound to the target compound is available, the protein-bound structure of the target compound can be predicted by aligning the conformation of the target compound on the known 3D structure of the reference. We developed the flexible alignment program fkcombu , which aligns the target compound based on atomic correspondences with the reference compound. The correspondences are obtained by the MCS (maximum common substructure) of 2D chemical structures, using our build-up algorithm (Kawabata, J.Chem.Info.Model. , 2011, 51 ,1775). The prediction performance was evaluated using many target-reference pairs of superimposed ligand 3D structures on the same protein in the PDB, with different ranges of chemical similarity. We found that the RMSD between the predicted and correct target conformations significantly correlates with the chemical similarities between target-reference molecules. Generally speaking, if the reference and target compounds have more than 70 % chemical similarity, then the average RMSD of 3D conformations is less than 2.0Å. The source codes of KCOMBU package are freely available. We also developed the server HOMCOS ( http://homcos.pdbj.org ) to search and model complex structures. The server separates component molecules of PDB files of complexes (such as proteins, nucleic acids, small chemical compounds), stores their binding relationships. It searches these molecules by BLAST and our chemical structure comparison program KCOMBU . Based on found similar complexes, simple template-based models of the complex can be generated.

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