Side rotamers

Figure 2-54. Using RAMSES, the two rotamers oftolane can be distinguished the planar rotamer is shown on the left-hand side, and the rotamer with the ring planes perpendicular to each other is on the right.

Dunbrack R L Jr and M Karplus 1993. Backbone-dependent Rotamer Library for Proteins. Applic to Side-chain Prediction. Journal of Molecular Biology 230 543-574. 

Side chain generation is often a source of error. It will be most reliable if certain rules of thumb are obeyed. Start with structurally conserved side chains and hold them fixed. Then look at the energy and entropy of rotamers for the remaining side chains. Conventional conformation search techniques are often used to place each side chain. 

A recent survey analyzed the accuracy of tliree different side chain prediction methods [134]. These methods were tested by predicting side chain conformations on nearnative protein backbones with <4 A RMSD to the native structures. The tliree methods included the packing of backbone-dependent rotamers [129], the self-consistent mean-field approach to positioning rotamers based on their van der Waals interactions [145],... 

FI Schrauber, F Eisenhaber, P Argos. Rotamers To be or not to be An analysis of ammo acid side-chain conformations m globular proteins. J Mol Biol 230 592-612, 1993. 

MJ Bower, FE Cohen, RL Dunbrack Jr. Prediction of protein side-chain rotamers from a backbone-dependent rotamer library A new homology modeling tool. J Mol Biol 267 1268-1282, 1997. 

RL Dunbrack, M Karplus. Pi ediction of protein side-chain conformations from a backbone conformation dependent rotamer library. J Mol Biol 230 543-571, 1993. 

C Wilson, LM Gregoret, DA Agard. Modeling side-chain conformation for homologous proteins using an energy-based rotamer search. J Mol Biol 229 996-1006, 1993. 

Analysis and prediction of side-chain conformation have long been predicated on statistical analysis of data from protein structures. Early rotamer libraries [91-93] ignored backbone conformation and instead gave the proportions of side-chain rotamers for each of the 18 amino acids with side-chain dihedral degrees of freedom. In recent years, it has become possible to take account of the effect of the backbone conformation on the distribution of side-chain rotamers [28,94-96]. McGregor et al. [94] and Schrauber et al. [97] produced rotamer libraries based on secondary structure. Dunbrack and Karplus [95] instead examined the variation in rotamer distributions as a function of the backbone dihedrals ( ) and V /, later providing conformational analysis to justify this choice [96]. Dunbrack and Cohen [28] extended the analysis of protein side-chain conformation by using Bayesian statistics to derive the full backbone-dependent rotamer libraries at all... 

As an example of analysis of side-chain dihedral angles, the Bayesian analysis of methionine side-chain dihedrals is given in Table 3 for the ri = rotamers. In cases where there are a large number of data—for example, the (3, 3, 3) rotamer—the data and posterior distributions are essentially identical. These are normal distributions with the averages and standard variations given in the table. But in cases where there are few data. 

Certain side-chain conformations are energetically mote favorable than others. Computer programs used to model protein structures contain rotamer libraries of such favored conformations. 

If the sequence of a protein has more than 90% identity to a protein with known experimental 3D-stmcture, then it is an optimal case to build a homologous structural model based on that structural template. The margins of error for the model and for the experimental method are in similar ranges. The different amino acids have to be mutated virtually. The conformations of the new side chains can be derived either from residues of structurally characterized amino acids in a similar spatial environment or from side chain rotamer libraries for each amino acid type which are stored for different structural environments like beta-strands or alpha-helices. 

Several remedies have been suggested for improving the PB based pKa prediction methods. Most of them are based on strategies that combine conformational flexibility with the PB calculation. You and Bashford included multiple conformers by systematically scanning the side chain torsion angles [107], Alexov and Gunner used Monte-Carlo protocol to sample positions of hydroxyl and other polar protons [1], This method, referred to as the multi-conformation continuum electrostatic (MCCE), was later extended to include rotamers for residues that have strong electrostatic... 

Fig. 3 Important 19F-labelled amino acids, (a) Compounds that are wo-steric to native amino acids can be incorporated into proteins biosynthetically, but they possess too many degrees of torsional freedom to be useful for ssNMR structure analysis, (b) In these artificial amino acids the 19F-reporter group is rigidly attached to the peptide backbone. They can be incorporated by solid-phase peptide synthesis, but some problems can arise due to racemisation (4F-Phg, 4CF3-Phg), steric hindrance of coupling (F3-Aib) or HF elimination (fluoro-Ala, F3-Ala). 4F-Phg is additionally problematic due to an ambiguity of the side-chain rotamer. The preferred 19F-labels for ssNMR structure analysis are CF3-Bpg and CF3-Phg (as suitable substitutes for Leu, lie, Met, Val and Ala), as well as F3-Aib and CF3-MePro...

It should be noted that this adduct is chiral and that the opposite enantiomer would result upon addition of the phosphine to the other CNO face, which corresponds basically to addition of the phosphine to the other side of the M=C bond. Predictably, the base is bound most strongly when the alkoxide is electron-withdrawing (e.g., OCMe(CF3)2), and is more strongly bound to W than to Mo. A relatively stable CNO adduct of the syn rotamer forms first when OR is OCMe(CF3)2, as it is virtually the only rotamer present (Kei-103), and as was shown later (see below), the rate of conversion of the syn to the anti rotamer... 

J. B. A. Ross, W. R. Laws, J. C. Sutherland, A. Buku, P. G. Katsoyannis, I. L. Schwartz, and H. R. Wyssbrod, Linked-function analysis of fluorescence decay kinetics Resolution of side-chain rotamer populations of a single aromatic amino acid in small polypeptides, Photochem. Photobiol. 44, 365-370 (1986). 

Young et have shown that the aromatic side chain of the two Phe-containing rotamers [cyclo(Phe-Pro) ... 

Iodinated contrast agents with polyhydroxylated carbon side-chains contain a number of asymmetric carbon atoms yielding numerous optical isomers which relate to each other as enantiomers or diastereoisomers. Sterically hindered non-asymmetric carbon or nitrogen atoms might result in additional asymmetry centres while the partial double bond character of the acyl-carbon-nitrogen bond of amide functions can lead to cisitrans isomerism. Such isomers are labelled rotamers when heating in solution is able to modify their ratio. Isomerism of iodixanol has been described by Priebe et al. [122], Fossheim et al. [123] and by Molander et al. [115]. 

Having established the origin of the rotamers Gl, G2 and G3, the splitting within each of these groups into further components due to the chiral centres in the amide side-chains was to be examined. These polyhydroxylated side-chains contain solely the threo (RS) form of 3-amino-butane-1,2,4-triol as a racemate (Fig. 19). Accordingly, from the possible 8 chiral centres only 4 have to be taken into consideration. These would lead - without considering other types of isomerism - to 16 isomers (8 pairs of isomers). Including (E)I(Z) isomerism, 48 isomers can be expected. 

Having identified 6 centres of chirality, i.e. 4 due to the side-chains and 2 due to the atropisomerism, a total of 64 optical isomers are possible within each of the rotamers Gl, G2, G3. However, this number is reduced to 16 configurations because of identities which can be visualized as follows The Fischer projections of the iotrolan molecule are split at the bridge into two halves to give the... 

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