The puckering free-energy surface of proline

Proline has two preferred puckering states, which are often characterized by the pseudorotation phase angle and amplitude. Although proline's five endocyclic torsion angles can be utilized to calculate the phase angle and amplitude, it is not clear if there is any direct correlation between each torsion angle and the proline-puckering pathway. Here we have designed five proline puckering pathways utilizing each torsion angle χj (j = 1∼5) as the reaction coordinate. By examining the free-energy surfaces of the five puckering pathways, we find they can be categorized into two groups. The χ2 pathway (χ2 is about the Cβ—Cγ bond) is especially meaningful in describing proline puckering: it changes linearly with the puckering amplitude and symmetrically with the phase angle. Our results show that this conclusion applies to both trans and cis proline conformations. We have also analyzed the correlations of proline puckering and its backbone torsion angles ϕ and ψ. We show proline has preferred puckering states a...

[1]  C. A. G. Haasnoot.  The conformation of six-membered rings described by puckering coordinates derived from endocyclic torsion angles , 1992 .

[2]  R. Improta,et al.  Understanding the role of stereoelectronic effects in determining collagen stability. 1. A quantum mechanical study of proline, hydroxyproline, and fluoroproline dipeptide analogues in aqueous solution. , 2001, Journal of the American Chemical Society.

[3]  Pinak Chakrabarti,et al.  C—H⋯O hydrogen bond involving proline residues in α-helices , 1998 .

[4]  D. Hamelberg,et al.  Entropic and surprisingly small intramolecular polarization effects in the mechanism of cyclophilin A. , 2012, The journal of physical chemistry. B.

[5]  Alexander D. MacKerell,et al.  Extending the treatment of backbone energetics in protein force fields: Limitations of gas‐phase quantum mechanics in reproducing protein conformational distributions in molecular dynamics simulations , 2004, J. Comput. Chem..

[6]  R. Wierenga,et al.  The planar conformation of a strained proline ring: A QM/MM study , 2006, Proteins.

[7]  Stephen C. Harvey,et al.  Ribose puckering: structure, dynamics, energetics, and the pseudorotation cycle , 1986 .

[8]  M. Schumacher,et al.  The Crystal Structure of the Collagen-like Polypeptide (Glycyl-4(R)-hydroxyprolyl-4(R)-hydroxyprolyl)9 at 1.55 Å Resolution Shows Up-puckering of the Proline Ring in the Xaa Position* , 2005, Journal of Biological Chemistry.

[9]  Alexander D. MacKerell,et al.  All-atom empirical potential for molecular modeling and dynamics studies of proteins. , 1998, The journal of physical chemistry. B.

[10]  E J Milner-White,et al.  Pyrrolidine ring puckering in cis and trans-proline residues in proteins and polypeptides. Different puckers are favoured in certain situations. , 1992, Journal of molecular biology.

[11]  Y. Kang.  Ring Flip of Proline Residue via the Transition State with an Envelope Conformation , 2004 .

[12]  Dennis M. Whitfield,et al.  Quantitative description of six-membered ring conformations following the IUPAC conformational nomenclature , 2001 .

[13]  J. Mccammon,et al.  Mechanistic Insight into the Role of Transition-State Stabilization in Cyclophilin A , 2008, Journal of the American Chemical Society.

[14]  R. Raines,et al.  Effect of 3-hydroxyproline residues on collagen stability. , 2003, Journal of the American Chemical Society.

[15]  V. Madison,et al.  Flexibility of the pyrrolidine ring in proline peptides , 1977 .

[16]  A. Aliev,et al.  Quantum mechanical and NMR studies of ring puckering and cis/trans-rotameric interconversion in prolines and hydroxyprolines. , 2009, The journal of physical chemistry. A.

[17]  Dongju Zhang,et al.  Structural model of silica nanowire assembled from a highly stable (SiO2)8 unit. , 2006, The journal of physical chemistry. B.

[18]  A. Aliev,et al.  Conformational analysis of L-prolines in water. , 2007, The journal of physical chemistry. B.

[19]  Young Kee Kang,et al.  Assessment of density functionals with long‐range and/or empirical dispersion corrections for conformational energy calculations of peptides , 2010, J. Comput. Chem..

[20]  Accurate calculations of free-energy differences by the distribution method. , 2008, The Journal of chemical physics.

[21]  Jack D. Dunitz,et al.  Approximate relationships between conformational parameters in 5- and 6-membered rings , 1972 .

[22]  Roland L. Dunbrack,et al.  Cis-Trans Imide Isomerization of the Proline Dipeptide , 1994 .

[23]  D. Pal,et al.  Cis peptide bonds in proteins: residues involved, their conformations, interactions and locations. , 1999, Journal of molecular biology.

[24]  D. Cremer,et al.  General definition of ring puckering coordinates , 1975 .

[25]  R. Berisio,et al.  Preferred proline puckerings in cis and trans peptide groups: Implications for collagen stability , 2001, Protein science : a publication of the Protein Society.

[26]  Susumu Uchiyama,et al.  Effect of hydration on the stability of the collagen-like triple-helical structure of [4(R)-hydroxyprolyl-4(R)-hydroxyprolylglycine]10. , 2005, Biochemistry.

[27]  M. Sundaralingam,et al.  Exact method for the calculation of pseudorotation parameters P, τm and their errors. A comparison of the Altona–Sundaralingam and Cremer–Pople treatment of puckering of five-membered rings , 1981 .

[28]  Adam K. Sieradzan,et al.  Determination of effective potentials for the stretching of C(α) ⋯ C(α) virtual bonds in polypeptide chains for coarse-grained simulations of proteins from ab initio energy surfaces of N-methylacetamide and N-acetylpyrrolidine. , 2012, Journal of chemical theory and computation.

[29]  K. Dill,et al.  The flexibility in the proline ring couples to the protein backbone , 2005, Protein science : a publication of the Protein Society.

[30]  Young Kee Kang,et al.  Cis−Trans Isomerization and Puckering of Pseudoproline Dipeptides , 2002 .

[31]  Donald Hamelberg,et al.  Resolving the complex role of enzyme conformational dynamics in catalytic function , 2012, Proceedings of the National Academy of Sciences.

[32]  Understanding free-energy perturbation calculations through a model of harmonic oscillators: theory and implications to improve the sampling efficiency by molecular simulation. , 2010, The Journal of chemical physics.

[33]  Y. Kang.  Puckering transition of proline residue in water. , 2007, The journal of physical chemistry. B.

[34]  H. Wennemers,et al.  Importance of ring puckering versus interstrand hydrogen bonds for the conformational stability of collagen. , 2011, Angewandte Chemie.

[35]  M. Sundaralingam,et al.  Conformational analysis of the sugar ring in nucleosides and nucleotides. A new description using the concept of pseudorotation. , 1972, Journal of the American Chemical Society.

[36]  D. Hamelberg,et al.  Reoptimization of the AMBER force field parameters for peptide bond (Omega) torsions using accelerated molecular dynamics. , 2009, The journal of physical chemistry. B.

[37]  H. Scheraga,et al.  Conformational analysis of the 20 naturally occurring amino acid residues using ECEPP. , 1977, Macromolecules.

[38]  Donald Hamelberg,et al.  Phosphorylation effects on cis/trans isomerization and the backbone conformation of serine-proline motifs: accelerated molecular dynamics analysis. , 2005, Journal of the American Chemical Society.

[39]  Y. Kang.  Ab initio and DFT conformational study of proline dipeptide , 2004 .

[40]  D. DeTar,et al.  Conformations of proline. , 1977, Journal of the American Chemical Society.

[41]  Conrad C. Huang,et al.  UCSF Chimera—A visualization system for exploratory research and analysis , 2004, J. Comput. Chem..

[42]  Kenneth S. Pitzer,et al.  The Thermodynamics and Molecular Structure of Cyclopentane1 , 1947 .

[43]  Y. Kang,et al.  Cis-trans isomerization and puckering of proline residue. , 2004, Biophysical chemistry.

[44]  Peter J. Reilly,et al.  Puckering Coordinates of Monocyclic Rings by Triangular Decomposition , 2007, J. Chem. Inf. Model..

[45]  G. N. Ramachandran,et al.  Studies on the conformation of amino acids. XII. Energy calculations on prolyl residue. , 1970, Biochimica et biophysica acta.