The structures and properties of unsolvated peptides large enough to possess secondary structure have been examined by experiments and simulations. Some of the factors that stabilize unsolvated helices and sheets have been identified. The charge, in particular, plays a critical role in stabilizing α-helices and destabilizing β-sheets. Some helices are much more stable in vacuum than in aqueous solution. Factors like helix propensity, context, and the incorporation of specific stabilizing interactions have been examined. The helix propensities in vacuum differ from those found in solution. Studies of the hydration of unsolvated peptides can be performed one water molecule at a time. The first few water molecules only bind weakly to unsolvated peptides, and they bind much more strongly to some conformations than to others. The most favorable binding locations are not the protonation sites, but clefts or pockets where a water molecule can establish a network of hydrogen bonds. Non-covalent interactions between secondary structure elements leads to the formation of tertiary structure. Helical peptides assemble into complexes with a variety of intriguing structures. The intramolecular coupling of helices to make antiparallel coiled-coil geometries has also been investigated with model peptides.

Helices and Sheets in vacuo

The effects of hydration are included in empirical conformational energy computations on oligopeptides by means of a modified hydration-shell model Free energy terms are introduced to account for “specific hydration” due to water–solute hydrogen bonding and for “nonspecific hydration” describing the interaction of the solute with water molecules in a first-neighbor shell The dielectric constant has been doubled (over the value used for calculations in the absence of water) to take into account the presence of solvent Computations were carried out for the N-acetyl-N′-methylamides of the 20 naturally occurring amino acids Conformational energy maps are compared with similar maps calculated in the absence of hydration Minimum-energy conformations are located and compared with the corresponding minima for unhydrated peptides in terms of ordering with respect to potential energy, the dihedral angles at the minima, and the presence of intramolecular hydrogen bonds The Boltzmann factors for various conformational regions are altered significantly on hydration in some cases These changes can be explained in terms of differences in the hydration free energy terms for various conformations

Model for the conformational analysis of hydrated peptides. Effect of hydration on the conformational stability of the terminally blocked residues of the 20 naturally occurring amino acids

The dynamics of a finite α-helix have been studied in the harmonic approximation by a vibrational analysis of the atomic motions about their equilibrium positions. The system were represented by an empirical potential energy function, and all degrees of freedom (bond lengths, bond angles, and torsional angles) were allowed to vary. The complete results were compared with a more restrictive model in which the peptide dihedral angle was kept rigid; also, a model potential excluding hydrogen bonds was examined. Thermal fluctuations in the backbone dihedral angles ϕ and ψ are 12° to 15°. The fluctuations of adjacent dihedral angles are highly correlated, and the correlation pattern is affected by the flexibility of the peptide dihedral angle. Time-dependent autocorrelations in the motion of ϕ and ψ appear to decay due to dephasing in less than 1 psec, while the motions of the carbonyl oxygen and amide hydrogens out of the peptide plane are more harmonic. Length fluctuations have been evaluated and exhibit a strong end effect; the calculated elastic modulus is in agreement with other values. Rigid and adiabatic total energy surfaces corresponding to dihedral angle rotations in the middle of the helix have been obtained and compared with the quadratic approximation to those surfaces. The magnitudes and correlations between the fluctuations obtained by averaging over the adiabatic energy surface most closely resemble the vibrational results. Of particular interest is the fact that hydrogen bonds play a relatively small role in the local dihedral angle fluctuations, though the hydrogen bonds are important in the energy of overall length changes.

Vibrational approach to the dynamics of an α‐helix

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Protein structure and function, from a colloidal to a molecular view

The helix–coil transitions for poly-L-lysine (PL) were investigated by the methods of spectropolarimetry, viscometry and potentiometric titration in 02M NaCl at different temperatures as well as in 02MNaBr, 1MKCl, and in mixtures of 02MNaCl or NaBr with methanol at room temperature The enthalpy and entropy differences between the helical and coillike states of uncharged PL molecules in 02M NaCl were determined from the potentiometric titration curves The cooperativity parameters σ for PL in different solvents were determined by two methods (from the sharpness of the transition and from the dependence of the intrinsic viscosity on the helical content in the transition region) In 02MNaCl σ has a value of (23 ± 05) × 10−4 and does not depend on temperature, ie, the cooperativity of the helix-coil transition, as for PGA, is mainly of an entropy origin (the initiating of the helical region is accompanied by the entropy decrease ΔSi = −12 eu/mole of helical regions) A comparison of the obtained results for PGA and PL with the molecular theories of the helix-coil transitions shows that the role of dipole-dipole interactions of nonneighboring peptide groups is greatly overestimated in these theories, leading to a considerable enthalpy contribution to the free energy of initiating helical regions which is not observed in the experiment

Thermodynamic parameters of helix-coil transition in polypeptide chains. II. Poly-L-lysine.

The Zimm–Bragg parameters s and σ for the helix‐coil transition in polyglycine and poly‐l‐alanine are calculated in terms of molecular quantities, based on our earlier formulation which is modified here to take effects at junctions between helical and coil sequences into account more properly The statistical weight of a helical sequence is computed for both regular and nonregular helices In the latter, the dihedral angles φ and ψ (and χ for alanine) near the ends of helical sequences differ from those in the interior; this diffuseness, which extends over about five residues at each end, reduces the values of σ by a factor of 1000−1008 The dihedral angles and the corresponding conformational energies of both regular and nonregular helices are obtained by energy minimization The entropy factor in the statistical weight of a helical sequence consisting of j residues [(j + 1) peptide units] is obtained from the second derivatives of the energy surface in the 2j‐dimensional space for both regular and non

Molecular Theory of the Helix‐Coil Transition in Polyamino Acids. II. Numerical Evaluation of s and σ for Polyglycine and Poly‐l‐alanine in the Absence (for s and σ) and Presence (for σ) of Solvent

Nobuhiro Ḡo

Papers

Molecular Theory of the Helix‐Coil Transition in Polyamino Acids. II. Numerical Evaluation of s and σ for Polyglycine and Poly‐l‐alanine in the Absence (for s and σ) and Presence (for σ) of Solvent