Solvation model induced structural changes in peptides. A quantum chemical study on Ramachandran surfaces and conformers of alanine diamide using the polarizable continuum model

Potential energy surfaces of the model peptide HCO‐L‐Ala‐NH2 were calculated using polarizable continuum model (PCM) for the description of aqueous solution at RHF/3‐21G, RHF/6‐31+G(d), and B3LYP/6‐31+G(d) levels of theory. Energy minima were optimized at all three levels as well as at B3LYP/PCM/6‐311++G(d,p) level of theory. Results were correlated to experimental data of protein structures retrieved from PDB SELECT. It is concluded that alanine residues of proteins are modeled better by PCM results than by gas‐phase calculations on the alanine diamide model (frequently called alanine dipeptide model). The currently available version of the PCM model implemented in Gaussian 03 provides a reasonable alternative to anticipate solvation effects without the computational costs of introducing explicit solvent molecules into the model system. Frequencies calculated at RHF/PCM/6‐31+G(d) and B3LYP/PCM/6‐31+G(d) levels of theory show high correlation; thus, RHF results have their own merit. © 2004 Wiley Periodicals, Inc. J Comput Chem 25: 1522–1531, 2004

[1]  U. Hobohm,et al.  Enlarged representative set of protein structures , 1994, Protein science : a publication of the Protein Society.

[2]  U. Hobohm,et al.  Selection of representative protein data sets , 1992, Protein science : a publication of the Protein Society.

[3]  A G Császár,et al.  Ab initio characterization of building units in peptides and proteins. , 1999, Progress in biophysics and molecular biology.

[4]  A. Perczel,et al.  Peptide models. 17. The role of the water molecule in peptide folding. An ab initio study on the right-handed helical conformations of N-formylglycinamide and N-formyl-L-alaninamide monohydrates [H(CONH-CHR-CONH)H·H2O; R = H or CH3] , 1995 .

[5]  J. Tomasi,et al.  Electrostatic interaction of a solute with a continuum. A direct utilizaion of AB initio molecular potentials for the prevision of solvent effects , 1981 .

[6]  Jacopo Tomasi,et al.  Continuum solvation models: A new approach to the problem of solute’s charge distribution and cavity boundaries , 1997 .

[7]  Leo Radom,et al.  Harmonic Vibrational Frequencies: An Evaluation of Hartree−Fock, Møller−Plesset, Quadratic Configuration Interaction, Density Functional Theory, and Semiempirical Scale Factors , 1996 .

[8]  P. Karplus.  Experimentally observed conformation‐dependent geometry and hidden strain in proteins , 1996, Protein science : a publication of the Protein Society.

[9]  Shuji Tomoda,et al.  Solvent effects on the φ–ψ potential surfaces of glycine and alanine dipeptides studied by PCM and I-PCM methods , 2002 .

[10]  T. Keiderling,et al.  Ab Initio Calculation of Amide Carbonyl Stretch Vibrational Frequencies in Solution with Modified Basis Sets. 1. N-Methyl Acetamide , 2001 .

[11]  J. Hirst,et al.  Density Functional Theory Vibrational Frequencies of Amides and Amide Dimers , 2002 .

[12]  Intrinsically stable secondary structure elements of proteins: a comprehensive study of folding units of proteins by computation and by analysis of data determined by X-ray crystallography. , 2003, Chemistry.

[13]  Caterina Benzi,et al.  Understanding the role of stereoelectronic effects in determining collagen stability. 2. A quantum mechanical/molecular mechanical study of (Proline-Proline-Glycine)(n) polypeptides. , 2002, Journal of the American Chemical Society.

[14]  Imre G. Csizmadia,et al.  Peptide models. 1. Topology of selected peptide conformational potential energy surfaces (glycine and alanine derivatives) , 1991 .

[15]  J. Tomasi,et al.  Ab initio study of ionic solutions by a polarizable continuum dielectric model , 1998 .

[16]  H. Bernhard Schlegel,et al.  Methods for optimizing large molecules. Part III. An improved algorithm for geometry optimization using direct inversion in the iterative subspace (GDIIS) , 2002 .

[17]  F E Cohen,et al.  Conformational attractors on the Ramachandran map. , 1999, Acta crystallographica. Section D, Biological crystallography.

[18]  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.

[19]  ANDRÁS PERCZEL,et al.  Peptide models. XXXIII. Extrapolation of low‐level Hartree–Fock data of peptide conformation to large basis set SCF, MP2, DFT, and CCSD(T) results. The Ramachandran surface of alanine dipeptide computed at various levels of theory , 2003, J. Comput. Chem..

[20]  G. N. Ramachandran,et al.  Conformation of polypeptides and proteins. , 1968, Advances in protein chemistry.

[21]  H. Yoshida,et al.  A NEW APPROACH TO VIBRATIONAL ANALYSIS OF LARGE MOLECULES BY DENSITY FUNCTIONAL THEORY: WAVENUMBER-LINEAR SCALING METHOD , 2002 .

[22]  P. Pulay.  Improved SCF convergence acceleration , 1982 .

[23]  Jon Baker,et al.  Direct Scaling of Primitive Valence Force Constants: An Alternative Approach to Scaled Quantum Mechanical Force Fields , 1998 .

[24]  David A. Dixon,et al.  Conformational Study of the Alanine Dipeptide at the MP2 and DFT Levels , 2002 .

[25]  Caterina Benzi,et al.  Quantum mechanical study of the conformational behavior of proline and 4R‐hydroxyproline dipeptide analogues in vacuum and in aqueous solution , 2002, J. Comput. Chem..

[26]  Sándor Suhai,et al.  Theoretical Study of Aqueous N-Acetyl-l-alanine N‘-Methylamide: Structures and Raman, VCD, and ROA Spectra , 1998 .

[27]  Peter Pulay,et al.  Geometry optimization by direct inversion in the iterative subspace , 1984 .

[28]  Sándor Suhai,et al.  N-Acetyl-L-alanine N'-methylamide: a density functional analysis of the vibrational absorption and vibrational circular dichroism spectra , 1996 .

[29]  Christian Silvio Pomelli,et al.  Recent Advances in the Description of Solvent Effects with the Polarizable Continuum Model , 1998 .

[30]  Jacopo Tomasi,et al.  A new integral equation formalism for the polarizable continuum model: Theoretical background and applications to isotropic and anisotropic dielectrics , 1997 .

[31]  A. Barth,et al.  What vibrations tell about proteins , 2002, Quarterly Reviews of Biophysics.

[32]  Alan Grossfield,et al.  Role of solvent in determining conformational preferences of alanine dipeptide in water. , 2004, Journal of the American Chemical Society.

[33]  Is there an excuse for the non-conformist? Notes on the calculated energies, atom–atom contacts and natural abundance of the different conformers of alanine in proteins , 2004 .

[34]  P. Pulay.  Convergence acceleration of iterative sequences. the case of scf iteration , 1980 .

[35]  J. Andrew McCammon,et al.  Comparison of Continuum and Explicit Models of Solvation: Potentials of Mean Force for Alanine Dipeptide , 1996 .

[36]  A. Rashin,et al.  alpha- and 3(10)-helix interconversion: a quantum-chemical study on polyalanine systems in the gas phase and in aqueous solvent. , 2001, Journal of the American Chemical Society.