Conformations of Amino Acids

Alanine 18 is the smallest chiral common amino acid. It has been the subject of many computational studies but we focus here on three recent reports. Csaszar identified 13 conformations of alanine and optimized the structures at HF/6-31G, HF/6-31H-I-G, B3LYP/6-31H-I-G, and MP2/6-311++G. The relative energies for some of the low lying conformations, computed with the latter three methods, are reported in Table 3.14. The two lowest energy conformations correspond with the two conformations identified in an earlier microwave experiment.  

In 2008, Alonso and coworkers reported a combined experimental and computational study of the conformations of cysteine. They located 11 low lying conformers at MP4/6-311-i i-G(d,p)//MP2/6-311-l-l-G(d,p), and the five lowest energy structures are shown in Table 3.15. Using laser ablation molecular beam Fourier transform microwave spectroscopy, they identified six conformers present in the gas phase. Comparing the computed rotational constants and nuclear quadrupole coupling tensor components with the experiment, they were able to decidedly match up all six experimental conformers with computed structures. Of the five low energy conformers listed in Table 3.15, four of them were identified in the experiment. 

Hints of these failures began with the increasing error in predicted bond dissociation energy with the size of the compound. This work by Curtiss et al. and Check and Gilbert was discussed in Section 3.1 and pointed toward some systemic problem of B3LYP. 

3-tetramethylbutane, and n-octane. The relative energy compnted with a variety of different methods is listed in Table 3.16. The branched isomer is more stable than the linear isomer, yet all of the DFT methods Grimme examined, inclnding the double hybrid B2PLYP functional, predict the opposite relative energy  

TABLE 3.16 Energy (kcal mol of 2,2,33-Tetramethylbutane Relative to Octane 

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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... 

Pullman, B., and A. Pullman. 1974. Molecular Orbital Calculations on the Conformation of Amino Acid Residues of Proteins. Adv. Protein Chem. 28, 347-526. 

Magnetic resonance techniques have again been popular for studying enzymes which are involved in phosphate hydrolysis and transfer. 31P or 19F N.m.r.1-2 and spinlabelling3 have all been used to study the interaction of substrates with these enzymes, while affinity labelling4 5 6 7 is another technique which has been used to obtain information about the sequence and conformation of amino-acid chains at the active sites of enzymes. Recently, these experimental methods have been applied to the study of cell membranes,6-7 and these are mentioned in a new series of books concerned with enzymes in biological membranes.8 A new journal, Trends in Biochemical Sciences, which contains concise, up-to-date reviews on these and other topics is published by Elsevier on behalf of the International Union of Biochemistry. 

Molecular Orbital Calculations on the Conformation of Amino Acid Residues of Proteins... 

The conformations of amino-acid side chains are unrestrained during refinement. In well-refined models, side-chain single bonds end up in staggered conformations. 

In medicinal chemistry we can use isolated, well-defined artificial peptides made from a few amino acid residues only, and which have a specific microstructure, to investigate the biological function of a selected peptide segment of a large protein (see also Chapter 1.2). It is, therefore, an important challenge in bioorganic chemistry to stabilize specific conformations of amino acids and small peptides to fix defined three-dimensional structures [2, 3]. 

After the finding of a sweet taste in L-Asp-L-Phe-OMe (aspartame) by Mazur et at. (6), a number of aspartyl dipeptide esters were synthesized by several groups in order to deduce structure-taste relationships, and to obtain potent sweet peptides. In the case of the peptides, the configuration and the conformation of the molecule are important in connection with the space-filling properties. The preferred conformations of amino acids can be shown by application of the extended Hiickel theory calculation. However, projection of reasonable conformations for di- and tripeptide molecules is not easily accomplished. 

Pullman B, Pullman A (1974) Molecular orbital calculations on the conformation of amino acid residues of proteins. Adv Protein Chem 28 347 - 526... 

In otherl c-nmr studies, the effect of pH on the structure of pheno-barbital and diphenylhydantoinland on the conformation of amino acids and peptides has been examined using the C-enriched drugs. 

Anderson DP (2004) BOINC a system for public-resource computing and storage. In 5th IEEE/ACM international workshop on grid computing. IEEE Comput Soc, Los Alamitos Janin J, Wodak S, Levitt M, Maigret B (1978) Conformation of amino acid sidechains in proteins. J Mol Biol 125 357-386... 

V. Sasisekharan, P. K. Ponnuswamy. Backbone and sidechain conformations of amino acids and amino acid residues in peptides. Biopolymers. 1970, 9, 1249-1256. 

J. Janin, S. Wodak, M. Levitt, B. Maigret. Conformations of amino acid side-chains in proteins./. Mol. Biol. 1978, 125, 357-386. 

Figure I. Non-bonding interactions associated with planar conformations of amino acid radicals...

Feeney, J., Hansen, P. E., and Roberts, G. . K. (1974). Chem. Comm. 465. Use of 1 3 C-1H Spin-Coupling Constants in the Determination of Side-Chain Conformations of Amino-Acids. 

The coupling constants between the a-prolon and the //-proton of amino acids indicated that the conformation of amino acids bound to the cobalt porphyrin was relatively fixed. 

Fig. 1 Amino acids and their respective chromophores. a Lowest energy conformers of amino acids at the MP2 level, b Lowest eneigy conformers of amino acids at the AMI level, c Chromophores of each amino acid studied...

Secondary (2°) structure of proteins The ordered arrangements (conformations) of amino acids in localized regions of a polypeptide or protein. 

Secondary (2 ) structure refers to the ordered arrangement (conformations) of amino acids in localized regions of a polypeptide or protein. The two most prevalent types of secondary structure are the a-helix and the /3-pleated sheet, both of which are stabilized by hydrogen bonding. In an a-helix, the carbonyl group of each peptide bond is hydrogen-bonded to the N — H group of the peptide bond four amino acids away from it. 

Takahara et al. [112,113] studied the effect of enantiomerism on the cmc of amino acid surfactant. The cmc of racemic compounds was slightly higher than for the corresponding optically pure isomer. This may result from the difference in the conformation of amino acid moieties in the micelles, due to intermolecular hydrogen bonding. 

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