Differential deuterium isotope shifts and one-bond 1H-13C scalar couplings in the conformational analysis of protein glycine residues

The one-bond deuterium isotope shift effect for glycine C alpha resonances exhibits a conformational dependence comparable to that of the corresponding 1JHC scalar coupling in both magnitude (approximately 11 Hz at 14.1 T) and dihedral angle dependence. The similarity in the conformational dependence of the 1JHC and deuterium isotope shift values suggests a common physical basis. Given the known distribution of (phi, psi) main-chain dihedral angles for glycine residues, the deuterium isotope shifts and the 1JHC scalar couplings can determine conformations in the left- and right-handed helical-to-bridge regions of the (phi, psi) plane to an accuracy of approximately 13 degrees. In the absence of stereochemical assignments, the differential deuterium isotope shifts and the 1JHC scalar couplings can be combined with limited independent structural information (e.g., the sign of phi) to determine the chirality of the deuterium substitution.     

Conformational analysis of carboxylate and carboxamide side-chains bound to cations

The known structures, both small as well as macromolecules, as stored in the respective databases, provide a wealth of information that, when properly rationalized, can be used in the design of new molecules. The engineering of metal-binding sites in proteins requires an understanding of the effect of such a binding on the ligand conformation. Here we present an analysis of the side-chain conformations of aspartic and glutamic acids, asparagine and glutamine bound to cations, in proteins. The most populated state of the chi 1 torsion angle for Asx (aspartate and asparagine) residues is g- (around 64 degrees) and is occupied by all groups that have another ligand two residues ahead of them. Co-ordinating residues that are sequentially well separated from other ligands (and most Glx (glutamate and glutamine) belong to this category) show a preference for the g+ or t state (dihedral angle near -60 and 180 degrees, respectively) as is normally observed. A chi 2 value close to, but less than 180 degrees, offers the minimum energy conformation for Glx, but another ligand closely in the sequence can force the torsion to be in a gauche form. A survey of small molecule structures involving Asx and Glx fragments show the terminal torsion to be centred at 0 degree. This observation is imitated by ligand Asx groups, whereas for Glx the angle veers towards the negative side. This statistical preference becomes less prominent when the cation is held in the less commonly observed anti geometry, and is lost completely when the residues are involved in anion binding. Cations exhibit an absolute preference to bind the oxygen that is on the same side as C alpha for the shorter side-chain, and the one eclipsing C beta for the longer chain. The shortest amino acid with a charged side-chain, Asp, shows very subtle conformational variations. For example, the distribution of chi 1 is not symmetrical about 180 degrees, and the g+ state (at -68(+/- 5) degrees) is the most stable of all on the basis of both steric as well as electrostatic grounds. Besides, the magnitude and the sign of chi 2 show strong dependence on the chi 1 values. Even for the longer Glu side-chain, a chi 2-angle in the g+ state necessitates the chi 1 also to reside in the g+ conformation. These mutual dependences of torsion angles in small molecule structures are also retained in proteins.(ABSTRACT TRUNCATED AT 400 WORDS)     

Helix-forming tendencies of amino acids depend on their sequence contexts: tripeptides AFG and FAG show incipient beta-bulge formation in their crystal structures

Many of the theoretical methods used for predicting the occurrence of alpha-helices in peptides are based on the helical preferences of amino acid monomer residues. In order to check whether the helix-forming tendencies are based on helical preferences of monomers only or also on their sequence contexts, we synthesized permuted sequences of the tripeptides GAF, GAV, and GAL that formed crystalline helices with near alpha-helical conformation. The tripeptides AFG and FAG formed good crystals. The x-ray crystallographic studies of AFG and FAG showed that though they contain the same amino acids as GAF but in different sequences, they do not assume a helical conformation in the solid state. On the other hand, AFG and FAG, which contain the same amino acids but in a different sequence, exhibit nearly the same backbone torsion angles corresponding to an incipient formation of a beta-bulge, and exhibit nearly identical unit cells and crystal structures. Based on these results, it appears that the helix-forming tendencies of amino acids depend on the sequence context in which it occurs in a polypeptide. The synthetic peptides AFG (L-Ala-L-Phe-Gly) and FAG (L-Phe-L-Ala-Gly), C14H19N3O4, crystallize in the orthorhombic space group P2(1)2(1)2(1), with a = 5.232(1), b = 14.622(2), c = 19.157(3) A, Dx = 1.329 g cm-3, Z = 4, R = 0.041 for 549 reflections for AFG, and with a = 5.488(2), b = 14.189(1), c = 18.562(1) A, Dx = 1.348 g cm-3, Z = 4, R = 0.038 for 919 reflections for FAG. Unlike the other tripeptides GAF, GGV, GAL, and GAI, the crystals of AFG and FAG do not contain water molecule, and the molecules of AFG aor FAG do not show the helical conformation. The torsion angles at the backbone of the peptide are psi 1 = 144.5(5) degrees; phi 2, psi 2 = -98.1(6) degrees, -65.2(6) degrees; phi 3, psi 13, psi 31 = 154.1(6) degrees, -173.6(6) degrees, 6.9(8) degrees for AFG; and psi 1 = 162.6(3) degrees; phi 2, psi 2 = -96.7(4) degrees, -46.3(4) degrees; phi 3, psi 13, psi 31 = 150.1(3) degrees, -168.7(3) degrees, 12.2(5) degrees for FAG. The conformation angles (phi, psi) for residues 2 and 3 for both AFG and FAG show incipient formation of an beta-bulge.     

Conformational changes due to vicinal glycosylation: the branched alpha-L-Rhap(1-2)[beta-D-Galp(1-3)]-beta-D-Glc1-OMe trisaccharide compared with its parent disaccharides

Conformations of the alpha-L-Rhap(1-2)-beta-D-Glc1-OMe and beta-D-Galp(1-3)-beta-D-Glc1-OMe disaccharides and the branched title trisaccharide were examined in DMSO-d6 solution by 1H-nmr. The distance mapping procedure was based on rotating frame nuclear Overhauser effect (NOE) constraints involving C- and O-linked protons, and hydrogen-bond constraints manifested by the splitting of the OH nmr signals for partially deuteriated samples. An "isotopomer-selected NOE" method for the unequivocal identification of mutually hydrogen-bonded hydroxyl groups was suggested. The length of hydrogen bonds thus detected is considered the only one motionally nonaveraged nmr-derived constraint. Molecular mechanics and molecular dynamics methods were used to model the conformational properties of the studied oligosaccharides. Complex conformational search, relying on a regular phi, psi-grid based scanning of the conformational space of the selected glycosidic linkage, combined with simultaneous modeling of different allowed orientations of the pendant groups and the third, neighboring sugar residue, has been carried out. Energy minimizations were performed for each member of the phi, psi grid generated set of conformations. Conformational clustering has been done to group the minimized conformations into families with similar values of glycosidic torsion angles. Several stable syn and anti conformations were found for the 1-->2 and 1-->3 bonds in the studied disaccharides. Vicinal glycosylation affected strongly the occupancy of conformational states in both branches of the title trisaccharide. The preferred conformational family of the trisaccharide (with average phi, psi values of 38 degrees, 17 degrees for the 1-->2 and 48 degrees, 1 degree for the 1-->3 bond, respectively) was shown by nmr to be stabilized by intramolecular hydrogen bonding between the nonbonded Rha and Gal residues.     

Side-chains in native and random coil protein conformations. Analysis of NMR coupling constants and chi1 torsion angle preferences

The behaviour of amino acid side-chains in proteins in solution has been characterised by analysing NMR 3JHalphaH beta coupling constants and crystallographic chi1 torsion angles. Side-chains both in the core of native folded proteins and in situations where there is an absence of close packing including the random coil state have been considered. An analysis of experimental 3JHalphaH beta coupling constant data for ten proteins shows that in the core of native proteins a very close similarity is observed between the chi1 conformations adopted in solution and in crystals. There is clear evidence, however, for significant motional averaging about the chi1 torsion angles in solution. Using a model of a Gaussian distribution about the average torsion angles the extent of these fluctuations has been quantified; the standard deviation for the motion is 26 degrees, the fluctuations about chi1 in the protein core being similar in size to those found for main-chain phi torsion angles in solution. From the distribution of chi1 torsion angles in a data base of protein crystal structures, torsion angle populations and coupling constants have been predicted for a random coil polypeptide. Significant variations in the chi1 distributions for different amino acids give differences in the predicted coupling constants; for 3JHalphaH beta, for example, values of 5.1 and 5.7 Hz are predicted for serine compared with 4.9 and 9.9 Hz for leucine. Experimental data for short unstructured peptides show an excellent agreement with the predictions, indicating that the overall chi1 distributions in protein crystals reflect the local preferences of the amino acids. Predictions from the protein data base therefore provide an important framework for interpreting experimental data for non-native protein conformations and for residues on the surface of folded proteins.     

Stereochemical punctuation marks in protein structures: glycine and proline containing helix stop signals

An analysis on the nature of alpha-helix stop signals has been carried out, using a dataset of 1057 helices identified from 250 high resolution (相似文献   

Prediction of conformational states of amino acids using a Ramachandran plot

(phi, psi) data from crystal structures of 221 proteins having high resolution and sequence similarity cut-off at the 25% level were analysed by dividing the Ramachandran plot in three regions representing three conformational states: (i) conformational state 1: conformations in the (phi, psi) range from (-140 degrees, -100 degrees) to (0 degrees, 0 degrees); (ii) conformational state 2: conformations with (phi, psi) from (-180 degrees, 80 degrees) to (0 degrees, 180 degrees); and (iii) conformational state 3: all the remaining conformations in the (phi, psi) plane which are not included in the above two conformational states. Normalized probability values of the occurrence of single amino acid residues in conformational regions 1-3 and similar values for dipeptides were calculated. Comparisons of single residue and dipeptide normalized probability values have shown that short-range interactions, although strong, destabilize conformational states of only 44 dipeptides out of the 400 x 9 possible states. However, dipeptide frequency values provide better resolving power than single-residue potentials when used to predict conformational states of residues in a protein from its primary structure. The simple approach used in the present study to predict conformational states yields an accuracy of > 70% for 14 proteins and an accuracy in the range of 50-70% for 247 proteins. Thus these studies point out yet another use of the Ramachandran plot and the role of tertiary interactions in protein folding.     

Design of peptides using alpha,beta-dehydro-residues: synthesis, crystal structure and molecular conformation of Boc-L-Val-delta Phe-delta Phe-L-Val-OCH3

The peptide Boc-L-Val-delta Phe-delta Phe-L-Val-OCH3 was synthesized by the azlactone method in solution phase, and its crystal and molecular structures were determined by x-ray diffraction method. Single crystals were grown by slow evaporation from a methanol/water solution at 6 degrees C. The crystals belong to an orthorhombic space group P212121 with a = 10.478 (6) A, b = 13.953 (I), c = 24.347 (2) and Z = 4. The structure was determined by direct methods and refined by least squares procedure to an R value of 0.052. The structure consists of a peptide and a water molecule. The peptide adopts two overlapping beta-turn conformations of Types II and I' with torsion angles: phi 1 = -54.8 (6) psi 1 = 130.5 (4), phi 2 = 65.8 (5), psi 2 = 12.8 (6), phi 3 = 79.4 (5), psi 3 = 3.9 (7) degrees. The conformation is stabilized by intramolecular hydrogen bonds involving Boc CO and NH of delta Phe3 and CO of Val1 and NH of Val4. The molecules are tightly packed in the unit cell. The crystal structure is stabilized by hydrogen bonds involving NH of delta Phe2 and CO of a symmetry related (x-1/2, 1/2-y, -z) delta Phe2. The solvent-water molecule forms two hydrogen bonds with peptide molecule involving NH of Val1 as an acceptor and another with CO of a symmetry related (1-x, y-1/2, 1/2 -z) delta Phe3 as a donor. These studies indicate that a tetrapeptide with two consecutive delta Phe residues sequenced with valines on both ends adopts two overlapping beta-turns of Types II and I'.     

Disallowed Ramachandran conformations of amino acid residues in protein structures

An analysis of the nature and distribution of disallowed Ramachandran conformations of amino acid residues observed in high resolution protein crystal structures has been carried out. A data set consisting of 110 high resolution, non-homologous, protein crystal structures from the Brookhaven Protein Data Bank was examined. The data set consisted of a total of 18,708 non-Gly residues, which were characterized on the basis of their backbone dihedral angles (phi, psi). Residues falling outside the defined "broad allowed limits" on the Ramachandran map were chosen and the reported B-factor value of the alpha-carbon atom was used to further select well defined disallowed conformations. The conformations of the selected 66 disallowed residues clustered in distinct regions of the Ramachandran map indicating that specific phi, psi angle distortions are preferred under compulsions imposed by local constraints. The distribution of various amino acid residues in the disallowed residue data set showed a predominance of small polar/charged residues, with bulky hydrophobic residues being infrequent. As a further check, for all the 66 cases non-hydrogen van der Waals short contacts in the protein structures were evaluated and compared with the ideal "Ala-dipeptide" constructed using disallowed dihedral angle (phi, psi) values. The analysis reveals that short contacts are eliminated in most cases by local distortions of bond angles. An analysis of the conformation of the identified disallowed residues in related protein structures reveals instances of conservation of unusual stereochemistry.     

Different types of interactions involving cysteine sulfhydryl group in proteins

Various types of interactions involving the sulfhydryl group of free cysteine residues have been analyzed using known protein structures. In a hydrogen bond the -SH group is more amenable to donating its proton to a carbonyl group, rather than acting as a proton acceptor. It rarely interacts with a carboxylate group, and is a poor ligand to bind an anionic substrate. It is quite prone to make contacts that are definitely non-hydrogen bond type. In the S...C=O interaction the S atom is placed on the face of an amide group (mostly from the main-chain, but there are cases from the side-chain also) close to the C atom. Cases of S...N interaction, where the S atom is on top of the N atom of another residue (both main-, as well as side-chains, including the guanidinium group) are also observed. A considerable number of Cys residues have aromatic residues as neighbors, and here too, the preferred mode of interaction is along the face. The intra-residue S...C=O interaction constrains the main-chain and side-chain torsion angles (psi and chi1), whereas the inter-residue interactions are non-local and stabilize the tertiary structure. The S...C=O interaction may have a role in lowering the pKa values of the Cys residues in enzyme active sites.     

Non-proline cis peptide bonds in proteins

In a non-redundant set of 571 proteins from the Brookhaven Protein Data Base, a total of 43 non-proline cis peptide bonds were identified. Average geometrical parameters of the well-defined cis peptide bonds in proteins determined at high resolution show that some parameters, most notably the bond angle at the amide bond nitrogen, deviate significantly from the corresponding one in the trans conformation. Since the same feature was observed in cis amide bonds in small molecule structures found in the Cambridge Structural Data Base, a new set of parameters for the refinement of protein structures containing non-Pro cis peptide bonds is proposed.A striking preference was observed for main-chain dihedral angles of the residues involved in cis peptide bonds. All residues N-terminal and most residues C-terminal to a non-Pro cis peptide bond (except Gly) are located in the beta-region of a phi/psi plot. Also, all of the few C-terminal residues (except Gly) located in the alpha-region of the phi/psi plot constitute the start of an alpha-helix in the respective structure. In the majority of cases, an intimate side-chain/side-chain interaction was observed between the flanking residues, often involving aromatic side-chains. Interestingly, most of the cases found occur in functionally important regions such as close to the active site of proteins. It is intriguing that many of the proteins containing non-proline cis peptide bonds are carbohydrate-binding or processing proteins. The occurrence of these unusual peptide bonds is significantly more frequent in structures determined at high resolution than in structures determined at medium and low resolution, suggesting that these bonds may be more abundant than previously thought. On the basis of our experience with the structure determination of coagulation factor XIII, we developed an algorithm for the identification of possibly overlooked cis peptide bonds that exploits the deviations of geometrical parameters from ideality. A few likely candidates based on our algorithm have been identified and are discussed.     

Motional dynamics of residues in a beta-hairpin peptide measured by 13C-NMR relaxation

Structurally characterizing partially folded peptides is problematic given the nature of their transient conformational states. 13C-NMR relaxation data can provide information on the geometry of bond rotations, motional restrictions, and correlated bond rotations of the backbone and side chains and, therefore, is one approach that is useful to assess the presence of folded structure within a conformational ensemble. A peptide 12mer, R1GITVNG7KTYGR12, has been shown to partially fold in a relatively stable beta-hairpin conformation centered at NG. Here, five residues, G2, V5, G7, Y10, G11, were selectively 13C-enriched, and 13C-NMR relaxation experiments were performed to obtain auto- and cross-correlation motional order parameters, correlation times, bond rotation angular variances, and bond rotational correlation coefficients. Our results indicate that, of the three glycines, G7 within the hairpin beta-turn displays the most correlated phi(t),psi(t) rotations with its axis of rotation bisecting the angle defined by the H-C-H bonds. These positively correlated bond rotations give rise to "twisting" type motions of the HCH group. V5 and Y10 phi,psi bond rotations are also positively correlated, with their CbetaCalphaH groups undergoing similar "twisting" type motions. Motions of near-terminal residues G2 and G11 are less restricted and less correlated and are best described as wobbling-in-a-cone. V5 and Y10 side-chain motions, aside from being highly restricted, were found to be correlated with phi,psi bond rotations. At 303 K, where the hairpin is considered "unfolded," the peptide exists in a transient, collapsed state because backbone and side-chain motions of V5, G7, and Y10 remain relatively restricted, unlike their counterparts in GXG-based tripeptides. These results provide unique information toward understanding conformational variability in the unfolded state of proteins, which is necessary to solve the protein folding problem.     

Notch4 and Wnt-1 proteins function to regulate branching morphogenesis of mammary epithelial cells in an opposing fashion

The ab initio folding problem can be divided into two sequential tasks of approximately equal computational complexity: the generation of native-like backbone folds and the positioning of side chains upon these backbones. The prediction of side-chain conformation in this context is challenging, because at best only the near-native global fold of the protein is known. To test the effect of displacements in the protein backbones on side-chain prediction for folds generated ab initio, sets of near-native backbones (< or = 4 A C alpha RMS error) for four small proteins were generated by two methods. The steric environment surrounding each residue was probed by placing the side chains in the native conformation on each of these decoys, followed by torsion-space optimization to remove steric clashes on a rigid backbone. We observe that on average 40% of the chi1 angles were displaced by 40 degrees or more, effectively setting the limits in accuracy for side-chain modeling under these conditions. Three different algorithms were subsequently used for prediction of side-chain conformation. The average prediction accuracy for the three methods was remarkably similar: 49% to 51% of the chi1 angles were predicted correctly overall (33% to 36% of the chi1+2 angles). Interestingly, when the inter-side-chain interactions were disregarded, the mean accuracy increased. A consensus approach is described, in which side-chain conformations are defined based on the most frequently predicted chi angles for a given method upon each set of near-native backbones. We find that consensus modeling, which de facto includes backbone flexibility, improves side-chain prediction: chi1 accuracy improved to 51-54% (36-42% of chi1+2). Implications of a consensus method for ab initio protein structure prediction are discussed.     

C-capping and helix stability: the Pro C-capping motif

Here we have performed a statistical analysis of the protein database to find new putative local C-terminal motifs in alpha-helices. Our analysis shows that certain combinations of X-Pro pairs (Asn, Cys, His, Phe, Tyr, Trp, Ile, Val and Leu), in which residue X is the C-cap and the Pro is at position C', are more abundant than expected. In those pairs, except for the aliphatic residues, the presence of the Pro residue at C' tends to restrict the phi and psi dihedral angles of the residue at position C-cap, around -130 degrees , 70 degrees , respectively. For the aromatic residues as well as for His, the chi1 angle is around -60 degrees and the edge of the His and aromatic rings are close to the carbonyl group of the residue i - 4. In all the pairs having the above dihedral angles for residue C-cap, the main-chain amino group of Pro at C' is close to the last three main-chain carbonyls of the alpha-helix. The above structural arrangements suggests the existence of a stabilising electrostatic interaction of the residues at positions C-cap and C' with the helix macrodipole. We have denominated this putative local motif, the Pro-capping motif. To asses its importance in helix stability we have analysed by nuclear magnetic resonance (NMR) and far-UV circular dichroism (CD) a set of polyalanine-based peptides containing two of the above pairs: His-Pro and Phe-Pro, as well as the corresponding controls. In the case of the His-Pro pair we have found NMR evidence for the formation of the Pro-capping motif in aqueous solution. CD analysis shows that the presence of a Pro residue alters the C-cap properties of the preceding amino acids in the case of His and Phe makes them more favourable. The Pro-capping motif with the appropriate sequence, determines the location of the C terminus of alpha-helices and stabilises the helical conformation having Pro as the C' residue.     

Design considerations and computer modeling related to the development of molecular scaffolds and peptide mimetics for combinatorial chemistry

A critical issue in drug discovery utilizing combinatorial chemistry as part of the discovery process is the choice of scaffolds to be used for a proper presentation, in a three-dimensional space, of the critical elements of structure necessary for molecular recognition (binding) and information transfer (agonist/ antagonist). In the case of polypeptide ligands, considerations related to the properties of various backbone structures (alpha-helix, beta-sheets, etc.; phi, psi space) and those related to three-dimensional presentation of side-chain moieties (topography; chi (chi) space) must be addressed, although they often present quite different elements in the molecular recognition puzzle. We have addressed aspects of this problem by examining the three-dimensional structures of chemically different scaffolds at various distances from the scaffold to evaluate their putative diversity. We find that chemically diverse scaffolds can readily become topographically similar. We suggest a topographical approach involving design in chi space to deal with these problems.     

Calculation of the conformation of stereo-regular, double-spiral polynucleotides

By the step-by-step selection method energetically optimal conformation of double-stranded polynucleotides were calculated proceeding from the conformations of mono-and dinucleotides. These structures were found to belong to the families of DNA A and B forms. The dependence of six torsion angles of the polynucleotide chain on the glycosidic angle chi was investigated. As a result certain areas admitting of double-helix polynucleotides with sugar C3-endo with chi = -80 degrees were established.     

Orientation of the saccharide chains of glycolipids at the membrane surface: conformational analysis of the glucose-ceramide and the glucose-glyceride linkages using molecular mechanics (MM3)

Preferred conformations of the saccharide-ceramide linkage of glucosylceramides with different ceramide structures (normal and hydroxy fatty acids) were investigated by molecular mechanics (MM3) calculations and compared with conformational features obtained for glucosylglycerolipids (diacyl and dialkyl analogues). Relaxed energy map calculations with MM3 were performed for the three bonds (C1'-O1-C1-C2, torsion angles phi, psi, and theta 1) of the glucose-ceramide/diglyceride linkage at different values of the dielectric constant. For the phi torsion of the glycosidic C1'-O1 bond the calculations show a strict preference for the +sc range whereas the psi/theta 1 energy surface is dependent on the structure of the lipid moiety as well as on the dielectric constant (epsilon). Calculations performed on glucosylceramide with normal and hydroxy fatty acids at epsilon = 4 (bilayer subsurface conditions) show three dominating conformers (psi/theta 1 = ap/-sc, -sc/ap, and ap/ap). The ap/-sc conformer, which represents the global energy minimum, is stabilized by polar interactions involving the amide group. The +sc rotamer of theta 1 is unfavored in sphingolipids due to a Hassel-Ottar effect involving the sphingosine O3 and O1 oxygen atoms. Comparative calculations on glycosylglycerolipid analogues (ester and ether derivatives) show a distinct preference for the ap rotamer of theta 1. An evaluation of the steric hindrance imposed by the surrounding membrane surface shows that in a bilayer arrangement the range of possible conformations for the saccharide-lipid linkage is considerably reduced. The significance of preferred conformations of the saccharide-ceramide linkage for the presentation and recognition of the saccharide chains of glycosphingolipids at the membrane surface is discussed.     

Comparison between the phi distribution of the amino acids in the protein database and NMR data indicates that amino acids have various phi propensities in the random coil conformation

It has been indicated that amino acids have various intrinsic phi and psi propensities, as demonstrated from the comparison between experimental secondary structure propensities and their relative statistical distribution in the protein database for the appropriate region of the Ramachandran plot. However, this does not eliminate the possibility that these experimental propensities are the result of context effects due to the secondary structure environment of the mutated position. To demonstrate that there are at least real intrinsic phi propensities, independent of context effects, we have used two different nuclear magnetic resonance parameters related to the phi dihedral angle (J3 alpha HN coupling constants and the chemical shift of the C alpha H proton), determined in random-coil tetra- and pentapeptides, and/or in proteins. Comparison of the experimentally determined values for these parameters with the theoretical ones determined from the analysis by different empirical and theoretical equations of the phi dihedral angle statistical distribution of the amino acids in the protein database, supports the idea that each amino acid has, at least, different phi intrinsic propensities. Consideration of all conformations, or only coil conformations, in the protein database produces similar results. The reasonable correlation between these experimental and theoretical data and the hydrogen-exchange data in random-coil peptides suggests that maximisation of hydrophobic surface-buried and hydrogen-bond formation with the solvent could be responsible for these different random-coil conformational preferences. Analysis of the intrinsic propensities for beta-strand, alpha-helix and polyproline II dihedral angles of the 20 amino acids in coil conformations, indicates that the side-chain of the amino acids is mainly determining the relative preferences for the phi angle.     

The solution conformations of amino acids from molecular dynamics simulations of Gly-X-Gly peptides: comparison with NMR parameters

The conformations that amino acids can adopt in the random coil state are of fundamental interest in the context of protein folding research and studies of protein-peptide interactions. To date, no detailed quantitative data from experimental studies have been reported; only nuclear magnetic resonance parameters such as chemical shifts and J coupling constants have been reported. These experimental nuclear magnetic resonance data represent averages over multiple conformations, and hence they do not provide unique structural information. I have performed relatively long (2.5 ns) molecular dynamics simulations of Gly-X-Gly tripeptides, surrounded by explicit water molecules, where X represents eight different amino acids with long side chains. From the trajectories one can calculate time averaged backbone chemical shifts and 3J(NH alpha) coupling constants and compare these with experimental data. These calculated quantities are quite close to the experimental values for most amino acids, suggesting that these simulations are a good model for the random coil state of the tripeptides. On the basis of my simulations I predict 3J(alphabeta) coupling constants and present dihedral distributions for the phi, psi, as well as chi1 and chi2 angles. Finally, I present correlation plots for these dihedral angles.