Homology modeling and molecular dynamics simulations of MUC1-9/H-2Kb complex suggest novel binding interactions

International audienceHuman MUC1 is over-expressed in human adenocarcinomas and has been used as a target for immunotherapy studies. The 9-mer MUC1-9 peptide has been identified as one of the peptides which binds to murine MHC class I H-2K. The structure of MUC1-9 in complex with H-2K has been modeled and simulated with classical molecular dynamics, based on the x-ray structure of the SEV9 peptide/H-2K complex. Two independent trajectories with the solvated complex (10 ns in length) were produced. Approximately 12 hydrogen bonds were identified during both trajectories to contribute to peptide/MHC complex, as well as 1-2 water mediated hydrogen bonds. Stability of the complex was also confirmed by buried surface area analysis, although the corresponding values were about 20% lower than those of the original x-ray structure. Interestingly, a bulged conformation of the peptide's central region, partially characterized as a -turn, was found exposed form the binding groove. In addition, P1 and P9 residues remained bound in the A and F binding pockets, even though there was a suggestion that P9 was more flexible. The complex lacked numerous water mediated hydrogen bonds that were present in the reference peptide x-ray structure. Moreover, local displacements of residues Asp4, Thr5 and Pro9 resulted in loss of some key interactions with the MHC molecule. This might explain the reduced affinity of the MUC1-9 peptide, relatively to SEV9, for the MHC class I H-2K

An enhanced memory TSK-type recurrent fuzzy network for real-time classification

An enhanced memory TSK-type recurrent fuzzy network (EM-TRFN) is proposed in this paper, suitable for modeling complex dynamic systems. Feedback connections, formulated using finite impulse response (FIR) synaptic filters, are employed in the network architecture, serving as internal memories of multiple past firing values, used to determine the current rule firings. Thus, high-order temporal capabilities are embedded in the network, rendering it capable of modeling highly complex nonlinear temporal processes. The structure of the EM-TRFN is evolved in an on-line fashion, with concurrent structure and parameter learning. The proposed network is combined with the predictive modular fuzzy system (PREMOFS), leading to an efficient system for on-line time-series classification. Simulations on a gait identification problem indicate the efficiency of the proposed system. © 2007 EUCA