The potential of mean force surface for the alanine dipeptide in aqueous solution: a theoretical approach

Abstract Results of an application of integral equation theory to the determination of the intramolecular potential of mean force for the alanine dipeptide. N-methyl alanine acetamide, in aqueous solution are presented. The calculations are based on Ornstein—Zernike-like equations for polar systems with an intramolecular superposition approximation. The solvated free energy surface for the dipeptide as a function of the dihedral angles φ and ψ (Ramachandran plot) is determined and compared with the vaccum surface calculations. Conformations that are essentially forbidden in vaccum are found to be significant in aqueous solution. The solvent contributions to the free energy surface are decomposed into enthalpic and entropic terms. Possible applications and extensions of the method are outlined.

[1]  M. Karplus,et al.  Protein dynamics in solution and in a crystalline environment: a molecular dynamics study. , 1982, Biochemistry.

[2]  F. Momany,et al.  Conformational transitions and geometry differences between low‐energy conformers of N‐acetyl‐N′‐methyl alanineamide: An ab initio study at the 4‐21G level with gradient relaxed geometries , 1984 .

[3]  B. Montgomery Pettitt,et al.  The interionic potential of mean force in a molecular polar solvent from an extended RISM equation , 1983 .

[4]  David Chandler,et al.  Statistical mechanics of chemical equilibria and intramolecular structures of nonrigid molecules in condensed phases , 1976 .

[5]  C. Tanford,et al.  Theory of Protein Titration Curves. I. General Equations for Impenetrable Spheres , 1957 .

[6]  Martin Karplus,et al.  SOLVATION. A MOLECULAR DYNAMICS STUDY OF A DIPEPTIDE IN WATER. , 1979 .

[7]  H. Umeyama,et al.  Molecular orbital study of the effects of ionic amino acid residues on proton transfer energetics in the active site of carboxypeptidase a , 1981 .

[8]  B. Montgomery Pettitt,et al.  Integral equation predictions of liquid state structure for waterlike intermolecular potentials , 1982 .

[9]  K. Kopple,et al.  Solvent-dependent conformational distributions of some dipeptides , 1980 .

[10]  M. Avignon,et al.  Une Méthode de Dosage des Isomères de Rotation des Dipeptides en Solution par Spectroscopie infrarouge , 1970 .

[11]  William L. Jorgensen,et al.  Energy profile for a nonconcerted SN2 reaction in solution , 1985 .

[12]  P. Bothorel,et al.  Conformational analysis of dipeptides in aqueous solution. II. Molecular structure of glycine and alanine dipeptides by depolarized rayleigh scattering and laser Raman spectroscopy , 1973, Biopolymers.

[13]  Peter A. Kollman,et al.  Quantum and molecular mechanical studies on alanyl dipeptide , 1984 .

[14]  J. Andrew McCammon,et al.  Diffusive langevin dynamics of model alkanes , 1979 .

[15]  M. Karplus,et al.  Role of Electrostatics in the Structure, Energy, and Dynamics of Biomolecules: A Model Study of N-Methylalanylacetamide , 1985 .

[16]  F. Gurd,et al.  Electrostatic effects in myoglobin. Hydrogen ion equilibria in sperm whale ferrimyoglobin. , 1974, Biochemistry.

[17]  D. Osguthorpe,et al.  Monte Carlo simulation of water behavior around the dipeptide N-acetylalanyl-N-methylamide. , 1980, Science.

[18]  Mihaly Mezei,et al.  Monte Carlo determination of the free energy and internal energy of hydration for the Ala dipeptide at 25.degree.C , 1985 .

[19]  B. Montgomery Pettitt,et al.  Application of an extended RISM equation to dipolar and quadrupolar fluids , 1982 .

[20]  D. Chandler,et al.  Theory of the hydrophobic effect , 1977 .