Collagen and component polypeptides: Low frequency and amide vibrations F. Fontaine-Vive a,b , F. Merzel c , M.R. Johnson a, * , G.J. Kearley d a Institut Laue Langevin, Boîte Postale 156, 38042 Grenoble Cedex 9, France b Radiation, Reactors and Radionuclides Department, Faculty of Applied Sciences, Delft University of Technology, Mekelweg 15, 2629 JB Delft, The Netherlands c National Institute of Chemistry, Hajdrihova 19, 1000 Ljubljana, Slovenia d Bragg Institute, Building 87, Australian Nuclear Science and Technology Organisation, PMB 1 Menai, NSW 2234, Australia article info Article history: Received 6 October 2008 Accepted 2 December 2008 Available online 10 December 2008 Keywords: DFT Collagen Amide bands Phonons Breathing modes Water dynamics abstract Collagen is a fibrous protein, which exists widely in the human body. The biomechanical properties of collagen depend on its triple helix structure and the corresponding low frequency vibrations. We use first-principles, density functional theory methods and analytical force fields to investigate the molecular vibrations of a model collagen compound, the results being validated by comparison with published, inelastic neutron scattering data. The results from these atomistic simulations are used at higher fre- quency to study the Amide I and V vibrations and therefore the vibrational signature of secondary and tertiary structure formation. In addition to collagen, its component homopolymers, poly-glycine and poly-proline are also studied. The Amide V vibration of glycine is strongly modified in going from the sin- gle helix of poly-glycine II to the triple helix of collagen. The collagen models are hydrated and this work allows us to discuss the relative merits of density functional theory and force field methods when tack- ling complex, partially crystalline systems. Ó 2008 Elsevier B.V. All rights reserved. 1. Introduction In biology, the hydrogen-bond is a corner stone of our under- standing of living materials [1,2]. Intermediate in strength between covalent bonds and inter-molecular interactions, they can confer stability on molecular assemblies such as proteins and DNA and yet allow these structures to dissociate or denature under specific conditions. Moreover, these bio-molecular systems are solvated by water molecules which form extended hydrogen-bond networks. Detailed understanding of the role of hydrogen-bonding in complex systems is difficult since crystallography gives accurate information on systems with long-range order with a precision that is inversely proportional to the size of the system. And yet a change in hydrogen-bond length by less than 0.1 Å can cause a pro- nounced change in the behaviour of the bond. Vibrational spectros- copy is a local probe of structure since the effective force constants of normal modes depend mainly on short range interactions. How- ever, exploiting vibrational spectra depends critically on being able link the modes to a structural model, typically through total energy calculations. Experimental input from structural and spectroscopic techniques and numerical or theoretical input from simulations must therefore be combined in the study of hydrogen-bonds in complex systems. In this paper, we extend recent work on hydrogen-bonded sys- tems, using a range of analytical and ab initio numerical methods, combined with inelastic neutron scattering, to collagen and its component amino acids in their polymeric, solid state conforma- tions. Collagen is the most abundant protein in mammals. It is tough and inextensible, with great tensile strength, and is the main component of cartilage, ligaments and tendons, bone and teeth. In nature, thirteen types of collagen are found and type I is the most abundant collagen of the human body. Type I collagen is consti- tuted almost entirely by three chains of amino acids, each chain having a repeating (Gly–X–Y) sequence where Gly is the amino acid glycine, and X and Y are respectively proline and hydroxypro- line. These three chains are wound together in a tight triple helix through hydrogen-bonds perpendicular to the helix axis. The conformation of the backbone of each strand of the collagen molecule is close to that of the left-handed helices poly-glycine-II (PG-II) and poly-proline-II (PP-II), super-coiled into right-handed triple-helices. The first synthesis of dried synthetic polypeptides (Pro–Pro–Gly) 10 was reported by Sakakibara et al. [3]. It contains approximately one water molecule per PPG triplet, equivalent to 7 g water/100 g completely dried (PPG) 10 . Fig. 1 illustrates the tri- ple helical structure of the dried (PPG) 10 . The most tightly bound water molecules form hydrogen-bonded bridges between carbonyl groups of two different helices. The triple helical arrangement is fa- voured by the presence of glycine at every third residue, reducing the steric hindrance and providing an inter-chain hydrogen-bond perpendicular to the helix axis. Previous studies on hydrogen-bonded molecular crystals showed advances in the use of density functional theory (DFT) methods in the analysis of inelastic neutron scattering (INS) data 0301-0104/$ - see front matter Ó 2008 Elsevier B.V. All rights reserved. doi:10.1016/j.chemphys.2008.12.005 * Corresponding author. E-mail address: johnson@ill.fr (M.R. Johnson). Chemical Physics 355 (2009) 141–148 Contents lists available at ScienceDirect Chemical Physics journal homepage: www.elsevier.com/locate/chemphys