We also included the reference selleck chemicals Rucaparib sequences of the 2006/2007 epidemic variants, two Netherlands 2006a strains (Terneuzen70/2006/NL and Yerseke38/2006/NL [46], accession nos. “type”:”entrez-nucleotide”,”attrs”:”text”:”EF126964″,”term_id”:”119393709″EF126964 and “type”:”entrez-nucleotide”,”attrs”:”text”:”EF126963″,”term_id”:”119393706″EF126963, respectively), two Netherlands 2006b strains (DenHaag89/2006/NL and Nijmegen115/2006/NL [46], accession nos. “type”:”entrez-nucleotide”,”attrs”:”text”:”EF126965″,”term_id”:”119393712″EF126965 and “type”:”entrez-nucleotide”,”attrs”:”text”:”EF126966″,”term_id”:”119393715″EF126966, respectively), and a 2006b strain from Kobe, Japan (Kobe034/2006/JP, accession no. “type”:”entrez-nucleotide”,”attrs”:”text”:”AB291542″,”term_id”:”126471123″AB291542).

All other reference sequences used in the present study were obtained from GenBank. Analysis of amino acid variation. Amino acid variations at individual positions of viral proteins were calculated according to the method described by Huang et al. (18) on the basis of Shannon’s equation (45): where H(i), p(xi), and i indicate the amino acid entropy score of a given position, the probability of occurrence of a given amino acid at the position, and the number of the positions, respectively. An H(i) score of zero indicates absolute conservation, whereas a score of 4.4 indicates complete randomness. The H(i) scores were expressed on the capsid structure constructed by the homology modeling method described below. Molecular modeling.

The crystal structure of the NoV capsid P domain of the GII/4 VA387 strain at a resolution of 2.00 ? (PDB code: 2OBS (4) was used as the modeling template. P domains of the GII/4 2006b strains have sequence similarities of greater than 90% to that of VA387, which are high enough to construct models with a root mean square distance of ~1 ? for the main chain between the predicted and actual structures (2). A three-dimensional (3-D) model of the P domain monomer of the earliest 2006b strain in Brefeldin_A Japan (Aich3/2006/JP) was constructed by using MOE-Align and MOE-Homology in the Molecular Operating Environment (MOE; Chemical Computing Group, Inc., Montreal, Quebec, Canada) as described previously (33, 47). The 3-D structure was thermodynamically optimized by energy minimization using the MOE and an AMBER99 force field (39). A physically unacceptable local structure of the optimized 3-D model was further refined on the basis of Ramachandran plot evaluation by using MOE. The 3-D model of the P-domain dimer was constructed by the superimposition the structures of the P-domain monomer on chains A and B of the NoV capsid oligomer (PDB code 1IHM) (40). Nucleotide sequence accession numbers.