Rotameric states

Here, the configuration integral Q has been split into tliree integrals the integration j is over all conformations where 71 is in the ith rotameric state. F is the configurational... 

Figure 7-1. The active site of CAII rendered from the crystal structure (PDB ID 2CBA [87]). All dotted lines correspond to hydrogen-bonding interactions with distances <3.5 A. El 17 and E106 are in close proximity to HI 19, and E106 also interacts with T199 through the presumed hydroxyl proton of T199 (not shown for clarity). H64 is resolved to partially occupy both the in and out rotameric states...

Concomitant changes are also evident in the various NBO indices of Table 3.26, including NRT bond order bee and ionicity ice Figure 3.69 illustrates, for example, how changes in bond length Rce are accurately tracked by the variations in NRT bond order over the entire set of rotameric states. 

L.133 Using two sets of backbone RDC data, collected in bacteriophage Pfl and bicelle media, they obtained order tensor parameters using a set of crystallographic coordinates for the structural model. This allowed the refinement of C -C bond orientations, which then provided the basis for their quantitative interpretation of C -H RDCs for 38 out of a possible 49 residues in the context of three different models. The three models were (A) a static xi rotameric state (B) gaussian fluctuations about a mean xi torsion and (C) the population of multiple rotameric states. They found that nearly 75% of xi torsions examined could be adequately accounted for by a static model. By contrast, the data for 11 residues were much better fit when jumps between rotamers were permitted (model C). The authors note that relatively small harmonic fluctuations (model B) about the mean rotameric state produces only small effects on measured RDCs. This is supported by their observation that, except for one case, the static model reproduced the data as well as the gaussian fluctuation model. 

Fig. 6. The rotamer toggle switch. Agonist binding leads to changes in the rotameric states of aromatic amino acids in TM6 resulting in a change in the angle of the helical kink formed by the highly conserved Pro2886 5. ...

In our simulations, we performed association studies to elucidate their role by selecting pairs of those hot spot residues that established a barnase-barstar contact in the bound complex. In these simulations, we studied what effect the side-chain conformation had on contact formation for certain hot spot residue pairs. A typical result is shown in Figure 8. Starting from the correct rotameric state for certain hot spot residue pairs with the rest of the proteins in their unbound conformations leads to improved contact formation in the initial docking phase. This effect is not observed when performing equivalent simulations with non-hot-spot interfacial residue pairs. 

A series of simulations starting from reverse initial conditions (protein structures in bound conformations with hot-spot residue pairs in unbound rotameric states) leads to impaired contact formation during the initial docking phase. These findings indicate, first, that the hot-spot residues can actively hinder or support contact formation and second, that a side-chain refinement protocol relying on specific side-chain rotameric states may well miss crucial structural detail in the interfacial region. 

Fig. 5.2. Active site of the P450 BM-3/NPG complex in (a) the low temperature X-ray conformation (PDB ljpz) representative of distal state where the NPG (shown in green) is distant from the heme iron, with Phe87 (shown in magenta) interposed between NPG and heme iron (shown in blue) and (b) the alternative active site of the conformation predicted by Jovanovic et al. representative of the proximal state where Phe87 has changed its rotameric state to allow NPG to approach the heme iron...

MacArthur MW, Thornton JM. Protein side-chain conformation a systematic variation of chi 1 mean values with resolution—a consequence of multiple rotameric states Acta Crystallogr D Biol Crystallogr 1999 55 994-1004. 

An interesting data structure, called flexibility tree, can be employed in the search for the docked complex structure and it allows to combine several flexibility techniques [95]. The data structure hierarchically encodes the flexibility of a protein in variables that allow several protein parts to experience different kinds of moves. Flexibility of domains may be described via normal mode or hinge motions, and side chains are allowed to explore rotameric states. Flexibility trees for protein and ligand are implemented in Flip Dock that provides a genetic algorithm to optimize the variables to gain an induced fit complex ]96]. 

Less straightforward is the treatment of spin labels that are bound to the protein via a flexible linker, where exchange between various rotameric states can occur. To account for the different contributions to the PRE that can arise from this type of exchange, an ensemble approach was developed that refines the structures against PREs in place of PRE-derived distances [363], improving the accuracy of structures... 

When motion effects are expected to be due to the existence ofdifierent conformations (multiple rotameric states significantly populated), rather to local fluctuations, they can also be accounted for with staggered-rotamer models [29], in which discrete probabilities for the different conformers are introduced. They are often used when describing amino acid side-chain torsion conformations. See, for instance. Ref [30] for a recent critical analysis of several models. 

The chemical structure and conformational characteristics of the chain have been considered in the analysis of local dynamics with the DRIS formalism. Statistical analysis of cis-PIP equilibrium structure and characteristics reveals that each of bond triplets separated by the double bond along the chain backbone, assume 12 rotameric states, characterized by strongly interdependent torsional angles, whereas successive triplets obey indej dent conformational energetics [110, 111]. The isomeric states of bond triplets ares ts-,s= g s. ... 

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