Adsorption of Ionic Peptides on Inorganic Supports Susanna Monti,* ,† Michele Alderighi, ‡ Celia Duce, ‡ Roberto Solaro, ‡ and Maria Rosaria Tine ´ ‡ Istituto per i Processi Chimico-Fisici (IPCF-CNR), Area della Ricerca, Via G. Moruzzi 1, I-56124 Pisa, Italy, and Dipartimento di Chimica e Chimica Industriale, UniVersita ` degli Studi di Pisa, Via Risorgimento 35, I-56126 Pisa, Italy ReceiVed: October 21, 2008; ReVised Manuscript ReceiVed: December 12, 2008 Molecular dynamics (MD) simulations were performed to investigate the adsorption mode of a short three- residue peptide, namely H-Lys-Glu-Lys-NH 2 , having only hydrophilic amino acids with alternating negative and positive charges, on titanium dioxide, muscovite mica, and graphite surfaces and to characterize its conformational behavior upon adsorption. In agreement with experimental data, the peptide and its aggregates can weakly adsorb on graphite, and strongly adsorb on both titanium dioxide and muscovite, engaging direct and indirect interactions (mediated by calcium and potassium ions) with the surface atoms through the amino acid side chains. 1. Introduction In recent years research in the field of supramolecular chemistry and molecular recognition has focused its attention on biomolecular systems with the ability to self-assemble and form supramolecular structures of various shapes and definite properties which make them a very viable means in optical, mechanical, electronic, and biomedical applications. 1-5 In particular, increasing effort is currently being devoted to creating new hybrid synthetic systems with multifunctional characteris- tics combining self-assembling peptides and metal, metal alloy, and/or semiconductor solid supports. 6-8 However, in order to tailor the structural and physicochemical properties of these inorganic surfaces and impart additional functionalities to the new materials, comprising high biocompatibility, it is essential to gain a detailed knowledge of the adsorption scenario and a clear understanding of how the peptide molecules combine and adsorb onto the solid supports. Extensive experimental studies have shed some light on the behavior of various amino acids, peptides and their aggregates, proteins, and other interesting biomolecular systems deposited on clean surfaces under controlled conditions, whereas only a few theoretical investigations have focused on these classes of compounds. 9-17 However, many aspects of the adsorption mechanism and the influence of the interface on the aggregation process are not yet clarified and remain the subject of some ambiguity. The aim of the present work is to provide a detailed description, at the atomic level, of the adsorption behavior of the H-Lys 1 -Glu 2 -Lys 3 -NH 2 peptide (from now on one letter code will be used for the amino acids as follows Lys ) K and Glu ) E), recently investigated in our group 18 on three different types of layers, namely rutile (1 1 0), muscovite (0 0 1), and highly oriented pyrolytic graphite (HOPG), and give, possibly, new insights in the role played by the solid supports estimating the peptide affinity for the examined materials. The choice of this kind of inorganic substrates was dictated by the fact that titanium-based materials have been extensively employed, for their advantageous mechanical and chemical properties such as tensile strength, fracture toughness, corrosion resistance, and biocompatibility, 19 in the creation of artificial biomimetic surfaces (obtained through the incorporation of bioadhesive motifs such as oligopeptides and proteins) able to adsorb on medical implants and regulate the biological response to the new material directly influencing implant biocompatibility. On the other hand, muscovite mica and HOPG are a popular choice for the study of interfacial phenomena, the former because its almost perfect cleavage along the (0 0 1) planes removes the complexities introduced by the surface roughness and the latter because its surface is highly ordered and chemically inert. Moreover, all of these supports are used in atomic force microscopy (AFM) measurements to characterize the aggregates, to image the structure of the systems with subnanometer resolution under physiological conditions, and to measure their interaction forces qualitatively. Indeed, AFM has proven to be an appropriate technique to depict different stages of the formation of self-complementary peptide aggregates on various supports 20 and to demonstrate their supramolecular organization. The paper is organized as follows. In section 2 the main characteristics of the three studied surfaces are briefly described. The computational procedure is accounted for in section 3, and the results of the various simulations for the adsorption of a small aggregate of the H-KEK-NH 2 peptide (Figure 1), made of two hydrogen bonded conformations, extracted from a previous MD study, 18 on the three interfaces are reported in section 4. 2. Molecular Models 2.1. Structure of the Supports. MuscoWite Mica. The starting structure used in our calculations was a model of the muscovite (0 0 1) surface, which was kindly provided to us by A. G. Kalinichev 21 together with the force field parameters to describe the interatomic interactions (CLAYFF force field 22,23 ). Briefly, the model was built by cleaving the monoclinic C2/c 2M 1 muscovite crystal structure, a 2:1 layered dioctahedral aluminosilicate (KAl 2 (Si 3 Al)O 10 (OH 2 )), along the (0 0 1) plane at the middle of the interlayer space. One mica (0 0 1) layer consists of one octahedral aluminum sheet sandwiched between two tetrahedral silicon/aluminum sheets, which expose the * Author to whom correspondence should be addressed. Phone: +39- 050-3152520. FAX +39-050-3152442. E-mail: s.monti@ipcf.cnr.it. † Istituto per i Processi Chimico-Fisici. ‡ Universita ` degli Studi di Pisa. J. Phys. Chem. C 2009, 113, 2433–2442 2433 10.1021/jp809297c CCC: $40.75  2009 American Chemical Society Published on Web 01/21/2009