Crystal and molecular structure of the dehydropeptide Ac-delta Phe-Val-delta Phe-NH-Me.

The dehydropeptide Ac-delta Phe-L-Val-delta Phe-NH-Me, containing two dehydrophenylalanine (delta Phe) residues, crystallizes from methanol/water in space group P212121, with a = 12.622 (1), b = 12.979 (1), and c = 15.733 (1) A. In the solid state, the molecular structure is characterized by the presence of two intramolecular hydrogen bonds which form two consecutive beta-bends. The (phi, psi) torsion angles of the three residues are very similar and close to the standard values of type III beta-bends, so the molecular conformation corresponds to an incipient right-handed 3(10)-helix, only slightly distorted. In the crystal, the molecules are linked by head-to-tail hydrogen bonds, thus forming continuous helical columns packed in antiparallel mode. There are no lateral hydrogen bonds; the only interactions are hydrophobic contacts between the apolar side chains of neighboring helical columns.     

The crystal structure of the alpha-cellobiose.2 NaI.2 H(2)O complex in the context of related structures and conformational analysis

The crystal structure of beta-D-glucopyranosyl-(1-->4)-alpha-D-glucopyranose (alpha-cellobiose) in a complex with water and NaI was determined with Mo K(alpha) radiation at 150 K to R=0.027. The space group is P2(1) and unit cell dimensions are a=9.0188, b=12.2536, c=10.9016 A, beta=97.162 degrees. There are no direct hydrogen bonds among cellobiose molecules, and the usual intramolecular hydrogen bond between O-3 and O-5' is replaced by a bridge involving Na+, O-3, O-5', and O-6'. Both Na+ have sixfold coordination. One I(-) accepts six donor hydroxyl groups and three C-H***I(-) hydrogen bonds. The other accepts three hydroxyls, one Na+, and five C-H***I(-) hydrogen bonds. Linkage torsion angles phi(O-5) and psi(C-5) are -73.6 and -105.3 degrees, respectively (phi(H)=47.1 degrees and psi(H)=14.6 degrees ), probably induced by the Na+ bridge. This conformation is in a separate cluster in phi,psi space from most similar linkages. Both C-6-O-H and C-6'-O-H are gg, while the C-6'-O-H groups from molecules not in the cluster have gt conformations. Hybrid molecular mechanics/quantum mechanics calculations show <1.2 kcal/mol strain for any of the small-molecule structures. Extrapolation of the NaI cellobiose geometry to a cellulose molecule gives a left-handed helix with 2.9 residues per turn. The energy map and small-molecule crystal structures imply that cellulose helices having 2.5 and 3.0 residues per turn are left-handed.     

Molecular structure of cyclo[-(D-Val-L-Hyi-L-Val-D-Hyi)2-] revealed by x-ray analysis.

The crystal structure of a synthetic analogue of valinomycin, cyclo[-(D-Val-L-Hyi-L-Val-D-Hyi)2-] (octa-meso-valinomycin) (I) (C40H68N4O12.1.5.C4H8O2, M(r) = 937.01 + 88.10), has been determined. Crystals grown from dioxane are monoclinic, space group P2(1)/a, with cell parameters a = 21.487 (8), b = 16.836 (5), c = 16.089 (4) A, beta = 111.70 (4), and Z = 4. The atomic coordinates for nonhydrogen atoms were refined in the anisotropic thermal motion approximation. H atom positions were included in the structure factor calculations at their geometrically expected positions. Values of the standard and weighted R factors after refinement are 0.11 and 0.13, respectively. The conformation of the depsipeptide crystallized from dioxane is different from that crystallized from chloroform (II). The molecule adopts a rectangular shape with two type IV beta-turns containing a hydrogen bond and possesses pseudorotational symmetry. The side chains are located on the molecular periphery. The orientation of the carbonyl groups of the molecule is not conducive for efficient metal-ion coordination and in the observed conformation cannot behave as an ionophore. In the crystal the molecules form infinite chains parallel to the c axis, and are stabilized by two intermolecular hydrogen bonds that are shorter and have better geometry than the intramolecular hydrogen bonds. A phi/psi plot for dodecadepsipeptides with a (DLLD)3 sequence has well-defined areas for Val and Hyi residues only in cases when the crystals have been grown from nonpolar or medium-polar solvents. The phi/psi plot for octadepsipeptides crystallized from chloroform (II) shows this behavior also.(ABSTRACT TRUNCATED AT 250 WORDS)     

Molecular dynamics of native protein. I. Computer simulation of trajectories

The motion of the atoms in the small protein bovine pancreatic trypsin inhibitor has been simulated for about 60 picoseconds using two different potential energy functions. In one known as HHL the hydrogen bond is purely electrostatic, in the other, known as L79, the hydrogen bond is a directional O . . . H interaction. The energy parameters and techniques used to obtain an accurate, well-equilibrated trajectory are described in detail. The trajectories calculated here with either potential are superior to those obtained in previous simulations on the same protein in that they treat hydrogen bonding realistically and remain closer to the native X-ray structure. Comparison of the two trajectories shows that the potential energy parameters have a significant effect on the shift from the X-ray structure, the distribution of (phi, psi) torsion angles, the pattern of hydrogen bonds and the accessible surface area of individual residues. The L79 potential with directional hydrogen bonds is used to simulate a longer 132 picosecond trajectory that is analysed in the accompanying paper.     

A sequence preference for nucleation of alpha-helix--crystal structure of Gly-L-Ala-L-Val and Gly-L-Ala-L-Leu: some comments on the geometry of leucine zippers

The synthetic peptide Gly-L-Ala-L-Val (C10H19N3O4.3H2O; GAV) crystallizes in the monoclinic space group P21, with a = 8.052(2), b = 6.032(2), c = 15.779(7) A, beta = 98.520(1) degree, V = 757.8 A3, Dx = 1.312 g cm-3, and Z = 2. The peptide Gly-L-Ala-L-Leu (C11H21N3O4.3H2O; GAL) crystallizes in the orthorhombic space group P212121, with a = 6.024(1), b = 8.171(1), c = 32.791(1) A, V = 1614 A3, Dx = 1.289 g cm-3, and Z = 4. Their crystal structures were solved by direct methods using the program SHELXS-86, and refined to an R index of 0.05 for 1489 reflections for GAV and to an R index of 0.05 for 1563 reflections for GAL. The tripeptides exist as a zwitterion in the crystal and assume a near alpha-helical backbone conformation with the following torsion angles: psi 1 = -150.7 degrees; phi 2, psi 2 = -68.7 degrees, -38.1 degrees; phi 3, psi 32 = -74.8 degrees, -44.9 degrees, 135.9 degrees for GAV; psi 1 = -150.3 degrees; phi 2, psi 2 = -67.7 degrees, -38.9 degrees; phi 3, psi 31, psi 32 = -72.2 degrees, -45.3 degrees, 137.5 degrees for GAL. Both the peptide units in both of the tripeptides show significant deviation from planarity [omega 1 = -171.3(6) degrees and omega 2 = -172.0(6) degrees for GAV; omega 1 = -171.9(5) degrees and omega 2 = -173.2(6) degrees for GAL]. The side-chain conformational angles chi 21 and chi 22 are -61.7(5) degrees and 175.7(5) degrees, respectively, for valine, and the side-chain conformations chi 12 and chi 23's are -68.5(5) degrees and (-78.4(6) degrees, 159.10(5) degrees) respectively, for leucine. Each of the tripeptide molecule is held in a near helical conformation by a water molecule that bridges the NH3+ and COO- groups, and acts as the fourth residue needed to complete the turn by forming two hydrogen bonds. Two other water molecules form intermolecular hydrogen bonds in stabilizing the helical structure so that the end result is a column of molecules that looks like an alpha-helix.     

Conformation of di-n-propylglycine residues (Dpg) in peptides: crystal structures of a type I' beta-turn forming tetrapeptide and an alpha-helical tetradecapeptide.

The crystal structures of two oligopeptides containing di-n-propylglycine (Dpg) residues, Boc-Gly-Dpg-Gly-Leu-OMe (1) and Boc-Val-Ala-Leu-Dpg-Val-Ala-Leu-Val-Ala-Leu-Dpg-Val-Ala-Leu-OMe (2) are presented. Peptide 1 adopts a type I'beta-turn conformation with Dpg(2)-Gly(3) at the corner positions. The 14-residue peptide 2 crystallizes with two molecules in the asymmetric unit, both of which adopt alpha-helical conformations stabilized by 11 successive 5 --> 1 hydrogen bonds. In addition, a single 4 --> 1 hydrogen bond is also observed at the N-terminus. All five Dpg residues adopt backbone torsion angles (phi, psi) in the helical region of conformational space. Evaluation of the available structural data on Dpg peptides confirm the correlation between backbone bond angle N-C(alpha)-C' (tau) and the observed backbone phi,psi values. For tau > 106 degrees, helices are observed, while fully extended structures are characterized by tau < 106 degrees. The mean tau values for extended and folded conformations for the Dpg residue are 103.6 degrees +/- 1.7 degrees and 109.9 degrees +/- 2.6 degrees, respectively.     

Conformation and hydrogen bonding of N-formylmethionyl peptides. Parallel beta-sheet in the crystal structure of N-formyl-L-methionyl-L-valine

Crystals of N-formyl-L-methionyl-L-valine (C11H20N2O)4S, M.W. = 276.3) are orthorhombic, space group )2(1)2(1)2(1) with cell constants at 294K of a = 4.851 (1), b = 14.925 (1), c = 19.745 (3) A, V = 1429.8 (1) A3, Z = 4 and observed (Dm) and calculated (Dx) of 1.49 and 1.488 g x cm-3, respectively. The crystal structure was solved using automatic diffractometer data (1260 reflections larger than or equal to 3 sigma) and refined to a final R-value of 0.035. This structure contains a short (2.626 (3) A) intermolecular hydrogen bond between the carboxyl OH and the N-acyl oxygen, a feature common to most N-acylamino acids and N-acylpeptides. The peptide is nearly planar (omega = 174.6 (5)); the values of psi 1, phi 2, psi 1T and psi 2T are, respectively, 131.8 (4) degrees, -139.9 (5) degrees, -39.3 (4) degrees and 142.1 (4) degrees. The methionine side chain is not zig-zag transplanar; the side chain torsion angles are: chi 1(1) = -60.0 (4) degrees, chi 2(1) = 176.0 (4) degrees and chi 3(1) = 71.8 (4) degrees. The two C gamma's for valine have psi 1-values of -64.4 (5) degrees and 173.7 (5) degrees. The formation of the parallel rather than antiparallel beta-sheet structure, the participation of the N-formyl group in the parallel beta-sheet and the use of C-H ... O hydrogen bonds to stabilize the beta-sheet are novel features found in this structure.     

Conformational features of C-glycosyl compounds: crystal structure and molecular modelling of "methyl C-gentiobioside"

The crystal of "methyl C-gentiobioside" (methyl 8,12-anhydro-6,7-dideoxy-D-glycero-D-gulo-alpha-D-gluco-trideca pyranoside) (C14H26O10) is triclinic, space group P1, with a = 1.0181 (6) nm, b = 0.8093 (5) nm, c = 0.5066 (4) nm, alpha = 96.03 (5) degrees, beta = 99.94 (5) degrees, gamma = 90.85 (5) degrees. The two D-glucose residues have the 4C1 conformation. The orientation of the beta-(1----6) linkage is characterized by torsion angles phi = 55.9 degrees, psi = 175.1 degrees, and omega = -63.9 degrees. The orientation of the primary hydroxyl group at the non-reducing residue is gauche-trans (omega' = -53.6 degrees). There is no intramolecular hydrogen bond. Molecules are held together by a network of hydrogen bonds involving all of the hydroxyl groups. This crystal structure is the first experimental characterization of a "C-disaccharide". Unlike methyl gentiobioside, which has a high level of conformational flexibility, the "C-disaccharide" has a restricted flexibility. Each of the low-energy conformers in vacuo has a value of phi centered about 60 degrees, in agreement with the solid state conformation, and the exo-anomeric effect is no longer predominant.     

The geometry of alpha-sheet: Implications for its possible function as amyloid precursor in proteins

alpha-sheet has been proposed as the main constituent of the prefibrillar intermediate during amyloid formation. Here the helical parameters of the alpha-sheet strand are calculated from average main-chain dihedral angles reported from molecular dynamics simulations. It is an almost linear polypeptide that forms a right-handed helix of about 100 A diameter, with 100 residues and a rise of 30 A per turn. The strands are curved but untwisted, which implies that neighboring strands need not coil to make interstrand hydrogen bonds. This suggests that compared to beta-sheets in native folded proteins, alpha-sheets can be larger and stack more easily to create extensive 3D blocks. It is shown that alpha-sheet is related to a category of structures termed "mirror" structures. Mirror structures have repetitive pairs of main-chain dihedral angles at residues i and i+1 that satisfy the condition phi(i) (+1) = -psi(i), psi(i) (+1) = -phi(i). They are uniquely identified by the two orientations of their peptide planes, specified by phi(i) and psi(i). Their side chains point alternately in opposite directions. Interestingly, their conformations are insensitive to phi(i) and psi(i) in that the pseudo dihedral angle formed by four consecutive C(alpha) atoms is always close to 180 degrees . There are two types: "beta-mirror" and "alpha-mirror" structure; beta-mirror structures relate to beta-sheet by small peptide plane rotations, of less than 90 degrees , while alpha-mirror structures are close to alpha-sheet and relate to beta-sheet by approximately 180 degrees peptide plane flips. Most mirror structures, and in particular the alpha-mirror, form wide helices with diameters 50-70 A. Their gentle curvature, and therefore that of the alpha-sheet, arises from the orientation of successive peptide units causing the difference in the bond angles at the C and N atoms of the peptide unit to gradually change the direction of the chain.     

Design of peptides with alpha,beta-dehydro-residues: synthesis, and crystal and molecular structure of a 3(10)-helical tetrapeptide Boc-L-Val-deltaPhe-deltaPhe-L-Ile-OCH3.

The peptide Boc-L-Val-deltaPhe-deltaPhe-L-Ile-OCH3 was synthesized using the azlactone method in the solution phase, and its crystal and molecular structures were determined by X-ray diffraction. Single crystals were grown by slow evaporation from solution in methanol at 25 degrees C. The crystals belong to an orthorhombic space group P2(1)2(1)2(1) with a = 12.882(7) A, b = 15.430(5) A, c = 18.330(5) A and Z = 4. The structure was determined by direct methods and refined by a least-squares procedure to an R-value of 0.073. The peptide adopts a right-handed 3(10)-helical conformation with backbone torsion angles: phi1 = 56.0(6)degrees, psi1 = -38.0(6)degrees, phi2 = -53.8(6)degrees, psi2 = 23.6(6)degrees, phi3 = -82.9(6)degrees, psi3 = -10.6(7)degrees, phi4 = 124.9(5)degrees. All the peptide bonds are trans. The conformation is stabilized by intramolecular 4-->1 hydrogen bonds involving Boc carbonyl oxygen and NH of deltaPhe3 and CO of Val1 and NH of Ile4. It is noteworthy that the two other chemically very similar peptides: Boc-Val-deltaPhe-deltaPhe-Ala-OCH3 (i) and Boc-Val-deltaPhe-deltaPhe-Val-OCH3 (ii) with differences only at the fourth position have been found to adopt folded conformations with two overlapping beta-turns of types II and III', respectively, whereas the present peptide adopts two overlapping beta-turns of type III. Thus the introduction of Ile at fourth position in a sequence Val-deltaPhe-deltaPhe-X results in the formation of a 3(10)-helix. The crystal structure is stabilized by intermolecular hydrogen bonds involving NH of Val1 and carbonyl oxygen of a symmetry related (-x, y - 1/2, 1/2 + z) deltaPhe2 and NH of deltaPhe2 with carbonyl oxygen of a symmetry related (x, y1/2, 1/2 + z) Ile4. This gives rise to long columns of helical molecules linked head to tail running along [010] direction.     

A molecular dynamics simulation of bacteriophage T4 lysozyme.

An analysis of a 400 ps molecular dynamics simulation of the 164 amino acid enzyme T4 lysozyme is presented. The simulation was carried out with all hydrogen atoms modeled explicitly, the inclusion of all 152 crystallographic waters and at a temperature of 300 K. Temporal analysis of the trajectory versus energy, hydrogen bond stability, r.m.s. deviation from the starting crystal structure and radius of gyration, demonstrates that the simulation was both stable and representative of the average experimental structure. Average structural properties were calculated from the enzyme trajectory and compared with the crystal structure. The mean value of the C alpha displacements of the average simulated structure from the X-ray structure was 1.1 +/- 0.1 A; differences of the backbone phi and psi angles between the average simulated structure and the crystal structure were also examined. Thermal-B factors were calculated from the simulation for heavy and backbone atoms and both were in good agreement with experimental values. Relationships between protein secondary structure elements and internal motions were studied by examining the positional fluctuations of individual helix, sheet and turn structures. The structural integrity in the secondary structure units was preserved throughout the simulation; however, the A helix did show some unusually high atomic fluctuations. The largest backbone atom r.m.s. fluctuations were found in non-secondary structure regions; similar results were observed for r.m.s. fluctuations of non-secondary structure phi and psi angles. In general, the calculated values of r.m.s. fluctuations were quite small for the secondary structure elements. In contrast, surface loops and turns exhibited much larger values, being able to sample larger regions of conformational space. The C alpha difference distance matrix and super-positioning analyses comparing the X-ray structure with the average dynamics structure suggest that a 'hinge-bending' motion occurs between the N- and C-terminal domains.     

Structural compromise of disallowed conformations in peptide and protein structures

Using a data set of 454 crystal structures of peptides and 80 crystal structures of non-homologous proteins solved at ultra high resolution of 1.2 A or better we have analyzed the occurrence of disallowed Ramachandran (phi, psi) angles. Out of 1492 and 13508 non-glycyl residues in peptides and proteins respectively 12 and 76 residues in the two datasets adopt clearly disallowed combinations of Ramachandran angles. These examples include a number of conformational points which are far away from any of the allowed regions in the Ramachandran map. According to the Ramachandran map a given (phi, psi) combination is considered disallowed when two non-bonded atoms in a system of two-linked peptide units with ideal geometry are prohibitively proximal in space. However, analysis of the disallowed conformations in peptide and protein structures reveals that none of the observations of disallowed conformations in the crystal structures correspond to a short contact between non-bonded atoms. A further analysis of deviations of bond lengths and angles, from the ideal peptide geometry, at the residue positions of disallowed conformations in the crystal structures suggest that individual bond lengths and angles are all within acceptable limits. Thus, it appears that the rare tolerance of disallowed conformations is possible by gentle and acceptable deviations in a number of bond lengths and angles, from ideal geometry, over a series of bonds resulting in a net gross effect of acceptable non-bonded inter-atomic distances.     

Influence of the environment in the conformation of alpha-helices studied by protein database search and molecular dynamics simulations

The influence of the solvent on the main-chain conformation (phi and Psi dihedral angles) of alpha-helices has been studied by complementary approaches. A first approach consisted in surveying crystal structures of both soluble and membrane proteins. The residues of analysis were further classified as exposed to either the water (polar solvent) or the lipid (apolar solvent) environment or buried to the core of the protein (intermediate polarity). The statistical results show that the more polar the environment, the lower the value of phi(i) and the higher the value of Psi(i) are. The intrahelical hydrogen bond distance increases in water-exposed residues due to the additional hydrogen bond between the peptide carbonyl oxygen and the aqueous environment. A second approach involved nanosecond molecular dynamics simulations of poly-Ala alpha-helices in environments of different polarity: water to mimic hydrophilic environments that can form hydrogen bonds with the peptide carbonyl oxygen and methane to mimic hydrophobic environments without this hydrogen bond capabilities. These simulations reproduce similar effects in phi and Psi angles and intrahelical hydrogen bond distance and angle as observed in the protein survey analysis. The magnitude of the intrahelical hydrogen bond in the methane environment is stronger than in the water environment, suggesting that alpha-helices in membrane-embedded proteins are less flexible than in soluble proteins. There is a remarkable coincidence between the phi and Psi angles obtained in the analysis of residues exposed to the lipid in membrane proteins and the results from computer simulations in methane, which suggests that this simulation protocol properly mimic the lipidic cell membrane and reproduce several structural characteristics of membrane-embedded proteins. Finally, we have compared the phi and Psi torsional angles of Pro kinks in membrane protein crystal structures and in computer simulations.     

Structure of papain refined at 1.65 A resolution

Papain is a sulfhydryl protease from the latex of the papaya fruit. Its molecules consist of one polypeptide chain with 212 amino acid residues. The chain is folded into two domains with the active site in a groove between the domains. We have refined the crystal structure of papain, in which the sulfhydryl group was oxidized, by a restrained least-squares procedure at 1.65 A to an R-factor of 16.1%. The estimated accuracy in the atomic co-ordinates is 0.1 A, except for disordered atoms. All phi/psi angles for non-glycine residues are found within the outer limit boundary of a Ramachandran plot and this provides another check on the quality of the model. In the alpha-helical parts of the structure, the C = O bonds are directed more away from the helix axis than in a classical alpha-helix, leading to somewhat longer hydrogen bonds, 2.98 A, compared to 2.89 A. The hydrogen-bonding parameters and conformational angles in the anti-parallel beta-sheet structure show a large diversity. Hydrogen bonds in the core of the sheet are generally shorter than those at the more twisted ends. The average value is 2.91 A. The hydrogen bond distance Ni+3-Oi in turns is relatively long and the geometry is far from linear. Hydrogen bond formation, therefore, is perhaps not an essential prerequisite for turn formation. Although the crystallization medium is 62% (w/w) methanol in water, only 29 out of 224 solvent molecules can be regarded with any certainty as methanol molecules. The water molecules play an important role in maintaining structural stability. This is specially true for internal water. Twenty-one water molecules are located in contact areas between adjacent papain molecules. It seems as if the enzyme is trapped in a grid of water molecules with only a limited number of direct interactions between the protein molecules. The residues in the active site cleft belong to the most static parts of the structure. In general, disorder in atomic positions increases when going from the interior of the protein molecule to its surface. This behavior was quantified and it was found that the point of minimum disorder is near the molecular centroid.     

Reduced representation model of protein structure prediction: statistical potential and genetic algorithms.

A reduced representation model, which has been described in previous reports, was used to predict the folded structures of proteins from their primary sequences and random starting conformations. The molecular structure of each protein has been reduced to its backbone atoms (with ideal fixed bond lengths and valence angles) and each side chain approximated by a single virtual united-atom. The coordinate variables were the backbone dihedral angles phi and psi. A statistical potential function, which included local and nonlocal interactions and was computed from known protein structures, was used in the structure minimization. A novel approach, employing the concepts of genetic algorithms, has been developed to simultaneously optimize a population of conformations. With the information of primary sequence and the radius of gyration of the crystal structure only, and starting from randomly generated initial conformations, I have been able to fold melittin, a protein of 26 residues, with high computational convergence. The computed structures have a root mean square error of 1.66 A (distance matrix error = 0.99 A) on average to the crystal structure. Similar results for avian pancreatic polypeptide inhibitor, a protein of 36 residues, are obtained. Application of the method to apamin, an 18-residue polypeptide with two disulfide bonds, shows that it folds apamin to native-like conformations with the correct disulfide bonds formed.     

Conformation and hydrogen bonding of N-formylpeptides: crystal and molecular structure of N-formyl-L-alanyl-L-aspartic acid.

Crystals of N-formyl-L-alanyl-L-aspartic acid (C8H11N2O6) grown from aqueous methanol solution are orthorhombic, space group, P2(1)2(1)2(1) with cell parameters at 294K of a = 13.619(2), b = 8.567(2), c = 9.583(3)A, V = 1118.1A3, M.W. = 232.2, Z = 4, Dm = 1.38 g/cm3 and Dx = 1.378 g/cm3. The crystal structure was solved by the application of direct methods and refined to an R value of 0.075 for 1244 reflections with I greater than or equal to 3 sigma collected on a CAD-4 diffractometer. The structure contains two short intermolecular hydrogen bonds: (i) between the C-terminal carboxyl OH and the N-acyl oxygen (2.624(3)A), a characteristic feature found in many N-acyl peptides and (ii) between the aspartic carboxyl OH. and the peptide oxygen OP1 (2.623(3)A). The peptide is nonplanar (omega = 165.5(6) degrees). The molecule takes up a folded conformation in contrast to N-formyl peptides which form extended beta-sheets; the values of phi 1, psi 1, phi 2, psi 2(1), and psi 2(2) are, respectively -65.7(6), 152.0(5), -107.2(5), 30.9(5), and -150.3(6). The aspartic acid side chain conformation is g- with chi 1 = 73.1(5). The formyl group, as expected, is transplanar [OF-CF-N1-CA1 = -4.0(8) degrees]. The presence of the short O-H ... O hydrogen bond emerges as a structural feature common to this peptide and several other N-formyl peptides. There are no C-H ... O hydrogen bonds in this structure.     

Synthesis and X-ray study of the 6-(N-pyrrolyl)purine and thymine derivatives of 1-aminocyclopropane-1-carboxylic acid.

The novel purine and pyrimidine derivatives of 1-aminocyclopropane-1-carboxylic acid 1 and 2 were obtained by alkylation of 6-(N-pyrrolyl)purine and thymine with methyl 1-benzamido-2-chloromethylcyclopropanecarboxylate. X-ray crystal structure analysis shows that the cyclopropane rings in 1 and 2 posses Z-configuration. The cyclopropane ring atoms and attached atoms of the benzamido and methoxycarbonyl moiety of both molecules are disposed perpendicularly to each other. The carbonyl oxygen of the methoxycarbonyl moiety adopts in both compounds a synperiplanar conformation with respect to the midpoint of the distal bond of the cyclopropane ring. The torsion angles Phi and psi for the 1-aminocyclopropane-1-carboxylic acid residue in 1 and 2 correspond to a folded conformation, while the torsion angles omega define antiperiplanar conformation. Intermolecular hydrogen bonds connect the molecules of 1 into dimers. Each dimer is hydrogen-bonded with four ethanol molecules, thus forming discrete unit. On the contrary, intermolecular hydrogen bonds link the molecules of 2 generating three-dimensional network.     

The normal modes of the gramicidin-A dimer channel.

The dynamics of the gramicidin-A dimer channel is studied in the harmonic approximation by a vibrational analysis of the atomic motions relative to their equilibrium positions. The system is represented by an empirical potential energy function, and all degrees of freedom (bonds lengths, bond angles, and torsional angles) are allowed to vary. The thermal fluctuations in the backbone dihedral angles phi and psi, atomic root mean square displacements, and the correlations between the different amide planes are computed. It is found that only adjacent dihedral psi i and phi i+1 are strongly correlated, while different hydrogen-bonded amide planes are only weakly correlated. Modes with relatively low vibrational frequencies (75-175 cm-1) make the dominant contributions to the carbonyl librations. The general flexibility of the structure and the role of carbonyl librations in the ion transport mechanism are discussed.     

Stereochemical quality of protein structure coordinates.

Methods have been developed to assess the stereochemical quality of any protein structure both globally and locally using various criteria. Several parameters can be derived from the coordinates of a given structure. Global parameters include the distribution of phi, psi and chi 1 torsion angles, and hydrogen bond energies. There are clear correlations between these parameters and resolution; as the resolution improves, the distribution of the parameters becomes more clustered. These features show a broad distribution about ideal values derived from high-resolution structures. Some structures have tightly clustered distributions even at relatively low resolutions, while others show abnormal scatter though the data go to high resolution. Additional indicators of local irregularity include proline phi angles, peptide bond planarities, disulfide bond lengths, and their chi 3 torsion angles. These stereochemical parameters have been used to generate measures of stereochemical quality which provide a simple guide as to the reliability of a structure, in addition to the most important measures, resolution and R-factor. The parameters used in this evaluation are not novel, and are easily calculated from structure coordinates. A program suite is currently being developed which will quickly check a given structure, highlighting unusual stereochemistry and possible errors.     

Design of peptides with branched beta-carbon dehydro-residues: syntheses, crystal structures and molecular conformations of two peptides, (I) N-Carbobenzoxy-DeltaVal-Ala-Leu-OCH3 and (II) N-Carbobenzoxy-DeltaIle-Ala-Leu-OCH3.

Highly specific structures can be designed by inserting dehydro-residues into peptide sequences. The conformational preferences of branched beta-carbon residues are known to be different from other residues. As an implication it was expected that the branched beta-carbon dehydro-residues would also induce different conformations when substituted in peptides. So far, the design of peptides with branched beta-carbon dehydro-residues at (i + 1) position has not been reported. It may be recalled that the nonbranched beta-carbon residues induced beta-turn II conformation when placed at (i + 2) position while branched beta-carbon residues induced beta-turn III conformation. However, the conformation of a peptide with a nonbranched beta-carbon residue when placed at (i + 1) position was not found to be unique as it depended on the stereochemical nature of its neighbouring residues. Therefore, in order to induce predictably unique structures with dehydro-residues at (i + 1) position, we have introduced branched beta-carbon dehydro-residues instead of nonbranched beta-carbon residues and synthesized two peptides: (I) N-Carbobenzoxy-DeltaVal-Ala-Leu-OCH3 and (II) N-Carbobenzoxy-DeltaIle-Ala-Leu-OCH3 with DeltaVal and DeltaIle, respectively. The crystal structures of peptides (I) and (II) have been determined and refined to R-factors of 0.065 and 0.063, respectively. The structures of both peptides were essentially similar. Both peptides adopted type II beta-turn conformations with torsion angles; (I): phi1 = -38.7 (4) degrees, psi1 = 126.0 (3) degrees; phi2 = 91.6 (3) degrees, psi2 = -9.5 (4) degrees and (II): phi1 = -37.0 (6) degrees, psi1 = 123.6 (4) degrees, phi2 = 93.4 (4), psi2 = -11.0(4) degrees respectively. Both peptide structures were stabilized by intramolecular 4-->1 hydrogen bonds. The molecular packing in both crystal structures were stabilized in each by two identical hydrogen bonds N1...O1' (-x, y + 1/2, -z) and N2...O2' (-x + 1, y + 1/2, -z) and van der Waals interactions.