Structural and Informatics Basis of Channel Protein Interactions

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Methods were developed for building tertiary structural models of channel proteins, by combining the inductive homology modeling method and the deductive molecular simulation for low-homologous regions. In particular, we developed a new model building method for flexible loop regions, based on the Force-Biased Multicanonical Molecular Dynamics (FB-McMD) with the implicit solvent model using the generalized Born approximation. This method could give us a precise protein model structure even for the flexible loop regions, and it was applied to modeling of actual channel proteins. In addition, protein functions with their sites and protein-protein interaction pairs were identified and predicted with the informatics technology using our new databases, eF-site and HINTdb, respectively.In order to analyze the molecular recognition of channel proteins, we have developed a new NMR analysis method, where the complexed structure is produced by molecular dynamics simulations using the cross saturation transfer and the residual dipolar coupling signals. This method was applied to build a complexed model between KcsA K^+-channel and agitoxin-2. Brownian dynamics simulation method was also developed for computing permeation of small ions and compounds through a channel protein.