Influence of hydration on the conformational stability and formation of bends in terminally blocked dipeptides

Abstract

SynopsisThe conformations of 23 terminally blocked dipeptide sequences were examined by conformational energy calculations that included the effects of the aqueous solvent.. Starting structures were derived from combinations of minimum-energy conformations of hydrated single residues. Their conformational energies were then minimized using the ECEPP potential (Empirical Conformational Energy Program for Peptides) with hydration included. Short-range interactions dominate in stabilizing the conformations of the hydrated dipeptides. Differences between conformational stabilities of hydrated and unhydrated dipeptides in many cases are due to the competition of solute-water and intramolecular hydrogen bonds. In other cases, perturbation of the hydration shell of the solute by close approach of solute atoms alters conformational preferences. Probabilities of formation of bends were calculated and compared to the corresponding quantities for unhydrated dipeptides and to those calculated from x-ray structures. For bends in dipeptides containing two nonpolar amino acids, computations omitting hydration yield better results. However, better agreement with experimental (x-ray) bend probabilities for dipeptides containing glycine or polar amino acids is obtained only in some sequences when hydration is included. The results are rationalized by the observation that, in proteins, bends containing nonpolar sequences occur on the inside, shielded from the solvent. Bends containing glycine or polar amino acids occur frequently on the surface of the protein, but they are not completely hydrated.

Conformational effects of substituting amino acids for glutamine-61 on the central transforming region of the P21 proteins.

“…This study also differs from the previous ones in that solvation is taken into account explicitly (22,23) because the sequence from residue 55 to residue 67 contains many polar residues and is very likely exposed to solvent (water). This treatment has been applied to computation of the structures of oligopeptides (23) and proteins (24) (25) and applied to computation of the structure of long polypeptide segments of interferon (24).…”

“…step, the energies of all minima obtained in step 3 were recomputed with the addition of a term for hydration (22)(23)(24)(25). All structures whose total conformational energies, including solvation free energy, lay within a cutoff of 5 kcal/mol of the energy of the global minimum were retained and combined with all of the single-residue minima for the next amino acid residue in the sequence, and the above four steps were reiterated.…”

An efficient, differentiable hydration potential for peptides and proteins

“…These radii were used in the determination of the values of the reduced radii ( R ; ) by means of eq. (11). The values for the empirical free energy densities, S j , in eq.…”

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

“…Hence, two alternative treatments of protein hydration have been developed. The first is a hydration-shell model in which empirical free energies of hydration are assigned to polar and nonpolar groups, and the overlap of hydration shells (leading to dehydration) tends to force nonpolar and polar groups to the inside and outside, respectively, of protein molecules (77,(116)(117)(118)224,239,240). A measure of the preference for the inside or outside is provided by a procedure that computes surface accessibility (157).…”