Nearest-neighbor interactions, protein

All the nearest-neighbor interactions between sialic acid or Neu5Ac2en and the protein are with totally conserved amino acids. Thus an inhibitor designed to bind only to the conserved active-site residues of neuraminidase would inhibit neuraminidase activity across all strains of influenza. This would enable the development of an antiviral drug that would affect the spread of viral replication potentially in three ways, i.e., transport through the protective mucosal layer, desialyation of freshly synthesized viral glycoproteins, and elution of progeny virions from infected cells. 

EXAFS studies have provided important clues on the coordination of the metal atoms. At the V K-edge the features of the absorption edge are consistent with V11 or Viv in a distorted octahedral environment with Fe, S, and O or N atoms as the nearest neighbors to the V atom. The Fe K-edge is dominated by Fe—S and Fe—Fe interactions consistent with the structure proposed for FeMoco. These results emphasize the structural similarity between the cofactor centers of MoFe and VFe proteins. 

FIGURE 77 Thermodynamic protein-ligand model adapted for the successive inter-molecular connections of metal ions to a one-dimensional multisite receptor (adapted from Piguet et al., 2005). /f is the absolute affinity of site / for the entering lanthanide R, and is the intramolecular intermetallic interaction between two nearest neighbors. 

Pathways [2, 50] is a semiempirical model which it is designed to reproduce electron transfer rates between cofactors in proteins [50, 151 ]. In essence. Pathways includes the contributions to the electronic tunneling from a stepwise path covering aU non-bonded interactions, as well as the bonded ones at the nearest neighbor level. Namely ... 

In addition to the HP model, several other low-resolution protein models have been developed to provide insight into the nature of protein folding. The AB model, used in the studies mentioned by Shakhnovich et al. and studied extensively by Socci and Onuchic, is similar in spirit to the HP model. The AB model is a three-dimensional lattice protein with 27 monomers. Each monomer is either of type A or type B, and the interaction energy between two nearest-neighbor, nonbonded monomers is Ec for an AA or BB pair, and E for an AB pair, where Ei < E < 0. In this scheme, like contacts are favored over unlike contacts, and there is an overall driving energy toward... 

One of the first off-lattice minimalist models was developed by Honeycutt and Thirumalai (HT) in 1990 to model a p-barrel motif. It models each amino acid as a single bead like those previously described, but it incorporates much more realistic energetic interactions by accounting for both nearest- and non-nearest-neighbor forces as well as for bond and torsion angles. The HT model includes three different types of residues hydrophobic (B), hydrophilic (L), and neutral (N). Consider the sequence for this 46-residue protein B9N3(LB)4N3B9N3(LB)4L. Its Hamiltonian is as follows. 

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