Conformation prediction, side

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],... 

The biological function of peptides and proteins depends on their native conformation. The side-chain functionalities of the a-amino acids that comprise peptides and proteins have profound effects on their properties. These functionalities reside in the 20 naturally occurring a-amino acids, which have different propensities for formation of the three major secondary structural conformations. 1 In addition to these naturally occurring a-amino acids whose primary structure enables the polypeptide to fold into a predictable secondary and tertiary structure, the incorporation of unnatural amino acids has opened important areas of research. 

Figure 12. Predicted side chain conformations of 17-keto steroids...

In the author s opinion the latter assumption, as stated by Mandel et al., appears misleading and if generalized could lead to erroneous predictions of "stable conformations of most polymers in the dissolved state. Discussion of the factors controlling chain conformations, considering side chain interactions without explicitly taking into account also the solvent — water — is in fact in the case of PMA, and obviously also in the case of many other water-soluble pol5miers and polyelectro-l5Ttes, an unjustified approximation. 

Figure 4. Theoretical CD spectra of poly[Ala -1-napAla] in a-helical conformation with the least-energy side-chain conformation predicted from the ECEPP energy calculation. Numbers in the figure indicate m.

Excimer Emission and CPF Spectra Fluorescence spectra of the two polypeptides in TMP solution are shown in Figure 7 (lower curves). Small excimer emissions are observed in the two polymers. The monomer/excimer intensity ratio was independent of the polymer concentration at least down to [pyr] = 1x10 mol L, suggesting an intramolecular character of the excimer. Since the interchromo-phore distances in the most probable conformations predicted from the conformational energy calculation are much longer than the exci-mer-forming distance, the excimers should be formed at the point where conformations of the main chain and/or the side chain are largely distorted. 

Most rotamer libraries are backbone-conformation-independent. In these libraries, the dihedral angles for side chains are averaged over all side chains of a given type and rotamer class, regardless of the local backbone conformation or secondary structure. These libraries include two in common use in side-chain conformation prediction methods, that of Ponder Richards and that of Tuffery et al. [165], It should be noted that the Ponder-Richards library is based on a very small sample of proteins and should not be used for conformation prediction (which was not its intended use anyway). The Tuffery library is based on 53 structures, which is also a very small sample compared to the PDB now available. Kono and Doi also published a rotamer... 

Side-chain conformation prediction is a combinatorial problem, since there are on the order of n ot possible conformations, where nrot is the average number of rotamers per side chain and N is the number of side chains. But in fact the space of conformations is much smaller than that, since side chains can only interact with a small number of neighbors, and in most cases clusters of interacting side chains can be isolated and each cluster can be solved separately [93, 165]. Also, many rotamers have prohibitively large interactions with the backbone and are at the outset unlikely to be part of the final predicted conformation. These can be eliminated from the search early on. 

Many standard search methods have been used in side-chain conformation prediction, including Monte Carlo simulation [176-178], simulated annealing [179], self-consistent mean field calculations [154, 173, 180], and neural networks [170]. Self-consistent mean field calculations represent each side chain as a set of conformations, each with its own probability. Each rotamer of each side chain has a certain probability, p(n). The total energy is a weighted sum of the interactions with the backbone and interactions of side chains with each other ... 

H. Kono, J. Doi. Energy minimization method using automata network for sequence and side-chain conformation prediction from given backbone geometry. Proteins. 1994, 19, 244-255. 

H. Kono, J. Doi. A new method for side-chain conformation prediction using a Hopfield network and reproduced rotamers. J. Comp. Chem. 1996, 17, 1667-1683. 

Wang, Q., Canutescu, A.A., and Dunbrack, R.L. (2008) SCWRL and MolIDE computer programs for side-chain conformation prediction and homology modeling. Nature Protocols, 3, 1832-1847. 

RC from Y strain Rb. sphaeroides contains spheroidene, a molecule belonging to the carotenoid family, whereas it is a 2,4 dihydroneurosporene in Rps. viridis. Both carotenoids are long polyenic chains which adopt a cis-conformation, predicted to be 15-15 by Raman spectroscopy for Rb. sphaeroides [21]. Electron density of Y strain Rb. sphaeroides RC clearly shows that the central region of the spheroidene molecule adopts the expected cis-conformation. The electron density assigned to spheroidene does not extend to both ends of the molecule and stereochemical constraints were applied to build up the extremities 8j. The central cis-bond is located at proximity of ring I of the so-called monomeric bacteriochlorophyll of the M side. 

D Cregut, J-P Liautard, L Chiche. Homology modeling of annexm I Implicit solvation improves side-chain prediction and combination of evaluation criteria allows recognition of different types of conformational eiTor. Protein Eng 7 1333-1344, 1994. 

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... 

Baumgartner and coworkers [145,146] study lipid-protein interactions in lipid bilayers. The lipids are modeled as chains of hard spheres with heads tethered to two virtual surfaces, representing the two sides of the bilayer. Within this model, Baumgartner [145] has investigated the influence of membrane curvature on the conformations of a long embedded chain (a protein ). He predicts that the protein spontaneously localizes on the inner side of the membrane, due to the larger fluctuations of lipid density there. Sintes and Baumgartner [146] have calculated the lipid-mediated interactions between cylindrical inclusions ( proteins ). Apart from the... 

Next, examine each cation s LUMO while displaying the cation as a space-filling model. Assuming that Br preferentially attacks the side of that is both less hindered and permits better overlap with the LUMO, predict the major product obtained from each cation conformer (if the two sides of C+ seem equally reactive, then predict a racemic product mixture). 

---