Dynamics and deformability of α-, 310- and π-helices

Tarun Jairaj Narwani, Pierrick Craveur, Nicolas K Shinada, Hubert Santuz, Joseph Rebehmed, Catherine Etchebest, Alexandre G. de Brevern

Abstract


Protein structures are often represented as seen in crystals as (i) rigid macromolecules (ii) with helices, sheets and coils. However, both definitions are partial because (i) proteins are highly dynamic macromolecules and (ii) the description of protein structures could be more precise. With regard to these two points, we analyzed and quantified the stability of helices by considering α-helices as well as 310- and π-helices. Molecular dynamic (MD) simulations were performed on a large set of 169 representative protein domains. The local protein conformations were followed during each simulation and analyzed. The classical flexibility index (B-factor) was confronted with the MD root mean square flexibility (RMSF) index. Helical regions were classified according to their level of helicity from high to none. For the first time, a precise quantification showed the percentage of rigid and flexible helices that underlie unexpected behaviors. Only 76.4% of the residues associated with α-helices retain the conformation, while this tendency drops to 40.5% for 310-helices and is never observed for π-helices. α-helix residues that do not remain as an α-helix have a higher tendency to assume β-turn conformations than 310- or π-helices. The 310-helices that switch to the α-helix conformation have a higher B-factor and RMSF values than the average 310-helix but are associated with a lower accessibility. Rare π-helices assume a β-turn, bend and coil conformations, but not α- or 310-helices. The view on π-helices drastically changes with the new DSSP (Dictionary of Secondary Structure of Proteins) assignment approach, leading to behavior similar to 310-helices, thus underlining the importance of secondary structure assignment methods.

https://doi.org/10.2298/ABS170215022N

This article was presented on the Belgrade Bioinformatics Conference 2016 (BelBI2016) [http://belbi2016.matf.bg.ac.rs/]

Received: February 15, 2017; Revised: May 2, 2017; Accepted: May 30, 2017; Published online: June 23, 23017

How to cite this article: Narwani TJ, Craveur P, Shinada NK, Santuz H, Rebehmed J, Etchebest C, de Brevern AG. Dynamics and deformability of α-, 310- and π-helices. Arch Biol Sci. 2018;70(1):21-31.


Keywords


helical local conformations; structural alphabet; molecular dynamics; disorder; flexibility

Full Text:

PDF

References


Kendrew JC, Bodo G, Dintzis HM, Parrish RG, Wyckoff H, Phillips DC. A three-dimensional model of the myoglobin molecule obtained by x-ray analysis. Nature. 1958;181(4610):662-6.

Eisenberg D. The discovery of the alpha-helix and beta-sheet, the principal structural features of proteins. Proc Natl Acad Sci U S A. 2003;100(20):11207-10.

Pauling L, Corey RB, Branson HR. The structure of proteins; two hydrogen-bonded helical configurations of the polypeptide chain. Proc Natl Acad Sci U S A. 1951;37(4):205-11.

Pauling L, Corey RB. The pleated sheet, a new layer configuration of polypeptide chains. Proc Natl Acad Sci U S A. 1951;37(5):251-6.

Miller SE, Watkins AM, Kallenbach NR, Arora PS. Effects of side chains in helix nucleation differ from helix propagation. Proc Natl Acad Sci U S A. 2014;111(18):6636-41.

Chakrabartty A, Kortemme T, Baldwin RL. Helix propensities of the amino acids measured in alanine-based peptides without helix-stabilizing side-chain interactions. Protein Sci. 1994;3(5):843-52.

Kumar S, Bansal M. Geometrical and sequence characteristics of alpha-helices in globular proteins. Biophys J. 1998;75(4):1935-44.

Malkov SN, Zivkovic MV, Beljanski MV, Stojanovic SD, Zaric SD. A reexamination of correlations of amino acids with particular secondary structures. Protein J. 2009;28(2):74-86.

Richardson JS, Richardson DC. Amino acid preferences for specific locations at the ends of alpha helices. Science. 1988;240(4859):1648-52.

Pal L, Chakrabarti P, Basu G. Sequence and structure patterns in proteins from an analysis of the shortest helices: implications for helix nucleation. J Mol Biol. 2003;326(1):273-91.

Presta LG, Rose GD. Helix signals in proteins. Science. 1988;240(4859):1632-41.

Aurora R, Srinivasan R, Rose GD. Rules for alpha-helix termination by glycine. Science. 1994;264(5162):1126-30.

Aurora R, Rose GD. Helix capping. Protein Sci. 1998;7(1):21-38.

Levitt M. Conformational preferences of amino acids in globular proteins. Biochemistry. 1978;17(20):4277-85.

Imai K, Mitaku S. Mechanisms of secondary structure breakers in soluble proteins. Biophysics. 2005;1:55-65.

Ho BK, Thomas A, Brasseur R. Revisiting the Ramachandran plot: hard-sphere repulsion, electrostatics, and H-bonding in the alpha-helix. Protein Sci. 2003;12(11):2508-22.

Ermolenko DN, Thomas ST, Aurora R, Gronenborn AM, Makhatadze GI. Hydrophobic interactions at the Ccap position of the C-capping motif of alpha-helices. J Mol Biol. 2002;322(1):123-35.

Prieto J, Serrano L. C-capping and helix stability: the Pro C-capping motif. J Mol Biol. 1997;274(2):276-88.

Dirr HW, Little T, Kuhnert DC, Sayed Y. A conserved N-capping motif contributes significantly to the stabilization and dynamics of the C-terminal region of class Alpha glutathione S-transferases. J Biol Chem. 2005;280(20):19480-7.

Kuhnert DC, Sayed Y, Mosebi S, Sayed M, Sewell T, Dirr HW. Tertiary interactions stabilise the C-terminal region of human glutathione transferase A1-1: a crystallographic and calorimetric study. J Mol Biol. 2005;349(4):825-38.

Donohue J. Hydrogen bonded helical configurations of the polypeptide chain. Proc Natl Acad Sci USA 1953;39:470-8.

Pal L, Basu G. Novel protein structural motifs containing two-turn and longer 3(10)-helices. Protein Eng. 1999;12(10):811-4.

Pal L, Basu G, Chakrabarti P. Variants of 3(10)-helices in proteins. Proteins. 2002;48(3):571-9.

Baker EN, Hubbard RE. Hydrogen bonding in globular proteins. Prog Biophys Mol Biol. 1984;44(2):97-179.

Barlow DJ, Thornton JM. Helix geometry in proteins. J Mol Biol. 1988;201(3):601-19.

Pal L, Dasgupta B, Chakrabarti P. 3(10)-Helix adjoining alpha-helix and beta-strand: sequence and structural features and their conservation. Biopolymers. 2005;78(3):147-62.

Karpen ME, de Haseth PL, Neet KE. Differences in the amino acid distributions of 3(10)-helices and alpha-helices. Protein Sci. 1992;1(10):1333-42.

Khrustalev VV, Barkovsky EV, Khrustaleva TA. The influence of flanking secondary structures on amino Acid content and typical lengths of 3/10 helices. Int J Proteomics. 2014;2014:360230.

Low BW, Baybutt RB. The p-helix -A hydrogen bonded configuration of the polypeptide chain. J Am Chem Soc 1952;74:5806.

Low BW, Greenville-Wells HJ. Generalized mathematical relationships for polypeptide chain helices. The coordinates of the p-helix. Proc Natl Acad Sci USA. 1953;39:785-801.

Ramachandran GN, Sasisekharan V. Conformation of polypeptides and proteins. Advan Protein Chem. 1968;23:283-438.

Rohl CA, Doig AJ. Models for the 3(10)-helix/coil, pi-helix/coil, and alpha-helix/3(10)-helix/coil transitions in isolated peptides. Protein Sci. 1996;5(8):1687-96.

Weaver TM. The pi-helix translates structure into function. Protein Sci. 2000;9(1):201-6.

Kumar P, Bansal M. Dissecting pi-helices: sequence, structure and function. FEBS J. 2015;282(22):4415-32.

Fodje MN, Al-Karadaghi S. Occurrence, conformational features and amino acid propensities for the pi-helix. Protein Eng. 2002;15(5):353-8.

Pollastri G, Przybylski D, Rost B, Baldi P. Improving the prediction of protein secondary structure in three and eight classes using recurrent neural networks and profiles. Proteins. 2002;47(2):228-35.

Wang S, Li W, Liu S, Xu J. RaptorX-Property: a web server for protein structure property prediction. Nucleic Acids Res. 2016;44(W1):W430-5.

Pancsa R, Raimondi D, Cilia E, Vranken WF. Early Folding Events, Local Interactions, and Conservation of Protein Backbone Rigidity. Biophys J. 2016;110(3):572-83.

Lee KH, Benson DR, Kuczera K. Transitions from alpha to pi helix observed in molecular dynamics simulations of synthetic peptides. Biochemistry. 2000;39(45):13737-47.

Millhauser GL. Views of helical peptides: a proposal for the position of 3(10)-helix along the thermodynamic folding pathway. Biochemistry. 1995;34(12):3873-7.

Millhauser GL, Stenland CJ, Bolin KA, van de Ven FJ. Local helix content in an alanine-rich peptide as determined by the complete set of 3JHN alpha coupling constants. J Biomol NMR. 1996;7(4):331-4.

Armen R, Alonso DO, Daggett V. The role of alpha-, 3(10)-, and pi-helix in helix-->coil transitions. Protein Sci. 2003;12(6):1145-57.

Goyal B, Kumar A, Srivastava KR, Durani S. Scrutiny of chain-length and N-terminal effects in α-helix folding: a molecular dynamics study on polyalanine peptides. J Biomol Struct Dyn. 2016;35(9):1923-35.

Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE. The Protein Data Bank. Nucleic Acids Res. 2000;28(1):235-42.

Fox NK, Brenner SE, Chandonia JM. SCOPe: Structural Classification of Proteins--extended, integrating SCOP and ASTRAL data and classification of new structures. Nucleic Acids Res. 2014;42(Database issue):D304-D309.

Chandonia JM, Hon G, Walker NS, Lo Conte L, Koehl P, Levitt M, Brenner SE. The ASTRAL Compendium in 2004. Nucleic Acids Res. 2004;32(Database issue):D189-D192.

Craveur P, Rebehmed J, de Brevern AG. PTM-SD: a database of structurally resolved and annotated posttranslational modifications in proteins. Database (Oxford). 2014;2014:bau041.

Pronk S, Pall S, Schulz R, Larsson P, Bjelkmar P, Apostolov R, Shirts MR, Smith JC, Kasson PM, van der Spoel D, Hess B, Lindahl E. GROMACS 4.5: a high-throughput and highly parallel open source molecular simulation toolkit. Bioinformatics. 2013;29(7):845-54.

van Gunsteren WF, Billeter SR, Eising AA, Hünenberger PH, Krüger P, Mark AE, Scott WRP, Tironi IG. Biomolecular Simulation: The GROMOS96 Manual and User Guide. Zürich, Switzerland: Vdf Hochschulverlag AG an der ETH Zürich; 1996. p. 1042.

Jorgensen WL, Madura JD. Quantum and statistical mechanical studies of liquids. 25. Solvation and conformation of methanol in water. J Am Chem Soc. 1983;105(6):1407-13.

Berendsen HJC, Postma JPM, van Gunsteren WF, DiNola A, Haak JR. Molecular dynamics with coupling to an external bath. J Chem Phys. 1984;81:3684-90.

Parrinello M, Rahman A. Polymorphic transitions in single crystals: A new molecular dynamics method. J Appl Phys. 1981;52(12):7182-90.

Hess B, Bekker H, Berendsen HJC, Fraaije JGEM. LINCS: a linear constraint solver for molecular simulations. J Comp Chem. 1997;18:1463-72.

Darden T, Perera L, Li L, Pedersen L. New tricks for modelers from the crystallography toolkit: the particle mesh Ewald algorithm and its use in nucleic acid simulations. Structure. 1999;7(3):R55-R60.

Bornot A, Etchebest C, de Brevern AG. Predicting protein flexibility through the prediction of local structures. Proteins. 2011;79(3):839-52.

Kabsch W, Sander C. Dictionary of protein secondary structure: pattern recognition of hydrogen-bonded and geometrical features. Biopolymers. 1983;22(12):2577-637.

de Brevern AG, Etchebest C, Hazout S. Bayesian probabilistic approach for predicting backbone structures in terms of protein blocks. Proteins. 2000;41(3):271-87.

Joseph AP, Agarwal G, Mahajan S, Gelly JC, Swapna LS, Offmann B, Cadet F, Bornot A, Tyagi M, Valadie H, Schneider B, Etchebest C, Srinivasan N, De Brevern AG. A short survey on protein blocks. Biophys Rev. 2010;2(3):137-47.

Leonard S, Joseph AP, Srinivasan N, Gelly JC, de Brevern AG. mulPBA: an efficient multiple protein structure alignment method based on a structural alphabet. J Biomol Struct Dyn. 2014;32(4):661-8.

Jallu V, Poulain P, Fuchs PF, Kaplan C, de Brevern AG. Modeling and molecular dynamics simulations of the V33 variant of the integrin subunit beta3: Structural comparison with the L33 (HPA-1a) and P33 (HPA-1b) variants. Biochimie. 2014;105:84-90.

Barnoud J, Santuz H, Craveur P, Joseph AP, Jallu V, de Brevern AG, Poulain P. PBxplore: A Tool To Analyze Local Protein Structure And Deformability With Protein Blocks [Internet]. 2017 May 10. [cited 2017 Jun 23]. Available from: http://biorxiv.org/content/early/2017/05/10/136408.full.pdf+html

Hartigan JA, Wong MA. A K-Means Clustering Algorithm. Journal of the Royal Statistical Society Series C (Applied Statistics). 1979;28(1):100-8.

Tyagi M, Bornot A, Offmann B, de Brevern AG. Analysis of loop boundaries using different local structure assignment methods. Protein Sci. 2009;18(9):1869-81.

Craveur P, Joseph AP, Esque J, Narwani TJ, Noel F, Shinada N, Goguet M, Leonard S, Poulain P, Bertrand O, Faure G, Rebehmed J, Ghozlane A, Swapna LS, Bhaskara RM, Barnoud J, Teletchea S, Jallu V, Cerny J, Schneider B, Etchebest C, Srinivasan N, Gelly JC, de Brevern AG. Protein flexibility in the light of structural alphabets. Front Mol Biosci. 2015;2:20.

Schlessinger A, Rost B. Protein flexibility and rigidity predicted from sequence. Proteins. 2005;61(1):115-26.

Schlessinger A, Yachdav G, Rost B. PROFbval: predict flexible and rigid residues in proteins. Bioinformatics. 2006;22(7):891-3.

Carugo O, Argos P. Correlation between side chain mobility and conformation in protein structures. Protein Eng. 1997;10(7):777-87.

de Brevern AG, Bornot A, Craveur P, Etchebest C, Gelly JC. PredyFlexy: flexibility and local structure prediction from sequence. Nucleic Acids Res. 2012;40(Web Server issue):W317-W322.

Patapati KK, Glykos NM. Three force fields' views of the 3(10) helix. Biophys J. 2011;101(7):1766-71.

de Brevern AG. Extension of the classical classification of beta-turns. Sci Rep. 2016;6:33191.

Richardson JS. The anatomy and taxonomy of protein structure. Adv Protein Chem. 1981;34:167-339.

Touw WG, Baakman C, Black J, te Beek TA, Krieger E, Joosten RP, Vriend G. A series of PDB-related databanks for everyday needs. Nucleic Acids Res. 2015;43(Database issue):D364-D368.

Craveur P, Joseph AP, Rebehmed J, de Brevern AG. beta-Bulges: extensive structural analyses of beta-sheets irregularities. Protein Sci. 2013;22(10):1366-78.

Mansiaux Y, Joseph AP, Gelly JC, de Brevern AG. Assignment of PolyProline II conformation and analysis of sequence--structure relationship. PLoS One. 2011;6(3):e18401.

Chebrek R, Leonard S, de Brevern AG, Gelly JC. PolyprOnline: polyproline helix II and secondary structure assignment database. Database (Oxford). 2014;2014:bau102.

Narwani TJ, Santuz H, Shinada N, Vattekatte AM, Ghouzam Y, Srinivasan N, Gelly JC, de Brevern AG. Recent advances on PolyProline II. Amino Acids. 2017;49(4):705-13.

Kumar P, Bansal M. Structural and functional analyses of PolyProline-II helices in globular proteins. J Struct Biol. 2016;196(3):414-25.

Bornot A, de Brevern AG. Protein beta-turn assignments. Bioinformation. 2006;1(5):153-5.

Luo J, Liu Z, Guo Y, Li M. A structural dissection of large protein-protein crystal packing contacts. Sci Rep. 2015;5:14214.

Carugo O, Argos P. Protein-protein crystal-packing contacts. Protein Sci. 1997;6(10):2261-3.

Offmann B, Tyagi M, de Brevern AG. Local Protein Structures. Current Bioinformatics. 2007;3:165-202.

Hornak V, Abel R, Okur A, Strockbine B, Roitberg A, Simmerling C. Comparison of multiple Amber force fields and development of improved protein backbone parameters. Proteins. 2006;65(3):712-25.

Pavlovic-Lazetic GM, Mitic NS, Kovacevic JJ, Obradovic Z, Malkov SN, Beljanski MV. Bioinformatics analysis of disordered proteins in prokaryotes. BMC Bioinformatics. 2011;12:66.


Refbacks

  • There are currently no refbacks.


Copyright (c) 2018 ARCHIVES OF BIOLOGICAL SCIENCES

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.