Side chain conformations

Miller, KE. Rich, D.H. Molecular Mechanics Calculations of Cyclosporin A Analogues. Effect of Chirality and Degree of Substitution on the Side-Chain Conformations of (2s, 3r, 4r, 6e)-3-Hydroxy-4-methyl-2-(methylamino)-6-octenoic Acid and Related Derivatives. 

Vasquez [121] reviewed and commented on various approaches to side chain modeling. The importance of two effects on side chain conformation was emphasized. The first effect was the coupling between the main chain and side chains, and the second effect was the continuous nature of the distributions of side chain dihedral angles for example. 

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],... 

M Vasquez. Modeling side-chain conformation. Curr Opm Stiaict Biol 6 217-221, 1996. JM Thornton. Disulphide bridges m globular proteins. J Mol Biol 151 261-287, 1981. 

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. 

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. 

MJ McGregor, SA Islam, MJE Sternberg. Analysis of the relationship between side-chain conformation and secondary structure m globular proteins. J Mol Biol 198 295-310, 1987. 

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. 

P Koehl, M Delarue. Application of a self-consistent mean field theory to predict protein side-chains conformation and estimate their conformational entropy. J Mol Biol 239 249-275, 1994. 

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... 

E Benedetti, G Morelh, G Nemethy, HA Scheraga. Statistical and energetic analysis of side-chain conformations m oligopeptides. Int J Peptide Pi otem Res 22 1-15, 1983. 

A second example is that of an Ala-to-Cys mutation, which causes the fonnation of a rare SH S hydrogen bond between the cysteine and a redox site sulfur and a 50 mV decrease in redox potential (and vice versa) in the bacterial ferredoxins [73]. Here, the side chain contribution of the cysteine is significant however, a backbone shift can also contribute depending on whether the nearby residues allow it to happen. Site-specific mutants have confirmed the redox potential shift [76,77] and the side chain conformation of cysteine but not the backbone shift in the case with crystal structures of both the native and mutant species [78] the latter can be attributed to the specific sequence of the ferre-doxin studied [73]. 

Certain side-chain conformations are energetically favorable... 

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

Coupling constants are routinely used to determine the side-chain conformation of amino acids in peptides and proteins. Whereas proteins nowadays are almost exclusively studied as C- and N-labeled isotopomers, peptides usually have these isotopes in natural abundance, i.e. the magnetically active heteronuclei are highly diluted. Most amino acids contain a methylene group at the ji-position for which the X angle is determined by the conformation of the Ca—Cp bond. Two vicinal Jhh coupling constants can be measured Ha to and H to Usually... 

Other than an effect on backbone solvation, side chains could potentially modulate PPII helix-forming propensities in a number of ways. These include contributions due to side chain conformational entropy and, as discussed previously, side chain-to-backbone hydrogen bonds. Given the extended nature of the PPII conformation, one might expect the side chains to possess significant conformational entropy compared to more compact conformations. The side chain conformational entropy, Y.S ppn (T = 298°K), available to each of the residues simulated in the Ac-Ala-Xaa-Ala-NMe peptides above was estimated using methods outlined in Creamer (2000). In essence, conformational entropy Scan be derived from the distribution of side chain conformations using Boltzmann s equation... 

Fig. 10. Electron density projection along -strand direction—hydrogen-bonding direction (a-axis) horizontal, and intersheet direction (c-axis) vertical—and skeletal models of polyGln8 (Q8) and polyGln45 (Q45) assemblies. The unit cell for both peptides was monoclinic, with lattice constants a = 9.73 A, b = 7.14 A, c = 8.16 A, and y = 95.7° for Q8, and a = 9.66 A, b = 7.10 A, c = 8.33 A, and y = 94.0° for Q45. The side chains are nearly overlapped in the hydrogen-bonding direction. This difference in side chain conformation and disorder likely accounts for the differences in observed intensity between their diffraction patterns.

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