Helix-Coil Stability Constants for the Naturally Occurring Amino Acids in Water. II. Characterization of the Host Polymers and Application of the Host-Guest Technique to Random Poly(hydroxypropylglutamine-co-hydroxybutylglutamine)

Dreele, P. H. Von; Lotan, Noah; Ananthanarayanan, V. S.; Andreatta, R. H.; Poland, Douglas; Scheraga, Harold A.

doi:10.1021/ma60022a008

Cited by 91 publications

(65 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…6 and 7. We note that such is not the case in most experiment and therefore simultaneous determination of the parameters and s as a function of temperature are generally precluded (23)(24)(25) and (͗k͗͘͞j͘) (s,) are those from Eqs. 6 and 7, given a set of s and .…”

Section: Methodsmentioning

confidence: 94%

Exploring Flory's isolated-pair hypothesis: Statistical mechanics of helix–coil transitions in polyalanine and the C-peptide from RNase A

Ohkubo

Brooks

2003

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

To evaluate Flory's isolated-pair hypothesis in the context of helical peptides, we explore equilibrium conformations of ␣-helixforming polypeptides as a function of temperature by means of replica exchange molecular dynamics in conjunction with the CHARMM͞GB implicit solvent force field and the weighted histogram analysis method. From these simulations, Zimm-Bragg parameters, s and , of Ac-Ala n -NMe are computed as a function of temperature. The values obtained for s(T) and (T) remain unchanged along the length of the polypeptide except for very short chains and yield results consistent with measurements based on short helix-forming peptides but suggest larger s values than anticipated from polymer-based measurements. From direct estimates of the density of states for Ac-Ala n-NMe (n ‫؍‬ 3-20) and peptide constructs based on the C peptide from RNase A, the conformational entropy is calculated versus temperature. The calculated S(T) shows a clear proportionality to the chain length over a wide range of temperature. This is observed in polypeptides with both significantly branched and simple methyl (alanine) side chains. These results provide evidence for the validity of Flory's isolated pair hypothesis, at least in the context of helical peptides and helix-to-coil transitions in these peptides.

show abstract

Section: Methodsmentioning

confidence: 94%

Exploring Flory's isolated-pair hypothesis: Statistical mechanics of helix–coil transitions in polyalanine and the C-peptide from RNase A

Ohkubo

Brooks

2003

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…18) by determining s and o for two different water-soluble homopolyamino acids and then synthesizing random copolymers of different compositions of these two amino acids. Using the parameters for one of the homopolymers, it was possible to compute those for the other homopolymer by applying the host-guest technique (and associated theory) to the copolymer data.…”

Section: Theoretical Melting Behavior Of a Random Copolymermentioning

confidence: 99%

Use of random copolymers to determine the helix-coil stability constants of the naturally occurring amino acids

Scheraga

1978

Pure and Applied Chemistry

Self Cite

110

View full text Add to dashboard Cite

AbstPact -Short-range interactions dominate in determining the conformational preferences of the amino acid residues in proteins, and a variety of procedures (based on this concept) have been developed to predict the conformational states of the residues of a protein molecule. This paper is concerned with two such conformational states, helical and non-helical (or coil) states; the relative preferences of each of the twenty naturally occurring amino acids for these two states can be expressed in terms of the Zirnm-Bragg parameters s and a. In principle, these parameters can be determined from experimental studies of the thermally-induced helix-coil transition in homopolymers of amino acids in water. However, since most homopolyamino acids are insoluble in water, or are not helical, or (if helical) do not melt between 0 and 100•c in water, resort is had to the host-guest technique in which a random copolymer of a water-soluble host residue and a small amount of a guest residue is prepared. Using the helix-coil transition curves of such a copolymer, and the values of s and a for the host homopolymer, it is possible to compute the values of s and a over the temperature range of 0-70°C for the guest residue which is, in turn, each of the twenty naturally occurring amino acids.In most cases, the random copolymers are prepared from their N-carboxyan~ hydrides, using suitable blocking groups to protect otherwise-reactive side-chain functional groups. The water-soluble copolymers are checked for the absence of racemization, a + ß shifts, etc., and for the required degree of randomness. For example, for methionine as a guest residue, cyanogen bromide cleavage of the polymer chain yields a series of oligopeptides which indicates that the methionine was incorporated randomly in the chain.When the resulting values of s and a are compared to the frequencies of occurrence of helical and non-helical conformations in proteins, a good correlation is obtained in most cases. In those cases where the correlation breaks down, the discrepancy provides information about the influence of specific long-range (e.g., electrostatic) interactions on the helical preferences of the given amino acid residues.The statistical weights deduced from the one-dimensional short-range interaction model are then incorporated with medium-and long-range interactions into a model to try to predict the three-dimensional structures of globular proteins.

show abstract

“…14), which characterize the transition curve, would appear to provide a quantitative basis for specifying the helix-making and breaking tendency of any amino acid in its corresponding homopolymer (and, therefore, in a protein, since short-range interactions dominate in both cases). Because of certain experimental problems discussed elsewhere" 15, 16 homopolymers cannot be used for this purpose, and resort is had instead to the use of random copolymers of two components -a helical host, for which a and s are known, and the guest residues; from the effect of increasing amounts of the guest residues on the helix-coil transition curve of the homopolymer of the host residues, it is possible to determine a and s for the guest residues" 15, 16 Thus far, these experiments have been carried out for the following guest residues: Gly17, Ala'8, Ser'9 and Leu20, and the results are shown in Table 1. It can be seen that Gly and Ser are helix-breakers, Gly more so than Ser (because s < I), and Ala and Leu are helix-makers, Leu more so than Ala.…”

Section: Quantitative Specification Of Hellx-mak1ng and Helix-breamentioning

confidence: 99%

On the dominance of short-range interactions in polypeptides and proteins

Scheraga¹

1973

Pure and Applied Chemistry

Self Cite

View full text Add to dashboard Cite

The development of the concept of the dominance of short-range interactions in polvpeptides and proteins is traced. It is shown that certain amino acid residucs have a preference to adopt the right-handed a-helical conformation while others exhibit a preference to participate in n-turns. These ideas are being applied in conformational energy calculations to try to determine the native conformations of proteins.

show abstract

Helix-Coil Stability Constants for the Naturally Occurring Amino Acids in Water. II. Characterization of the Host Polymers and Application of the Host-Guest Technique to Random Poly(hydroxypropylglutamine-co-hydroxybutylglutamine)

Cited by 91 publications

References 0 publications

Exploring Flory's isolated-pair hypothesis: Statistical mechanics of helix–coil transitions in polyalanine and the C-peptide from RNase A

Exploring Flory's isolated-pair hypothesis: Statistical mechanics of helix–coil transitions in polyalanine and the C-peptide from RNase A

Use of random copolymers to determine the helix-coil stability constants of the naturally occurring amino acids

On the dominance of short-range interactions in polypeptides and proteins

Contact Info

Product

Resources

About