In January 2006, I was employed by the Institute of Organic Chemistry and Biochemistry of the Academy of Sciences of the Czech Republic, with the purpose of developing, as an independent researcher, a line of research concerning the theoretical study on isolated polypeptides. This same year I co-directed the Diploma Thesis of a chemistry student of the Charles University of Prague. My first paper as corresponding author concerns the pioneer study of isolated small peptides by means of a new DFT method (DFT-D, Density Functional Theory with the inclusion of a empirical dispersion term) (Valdés et al. J. Phys. Chem. A 2007, 111, 1146). The results obtained are essential for this field of research since this method has been proven to be suitable for the study of medium-size systems (e.g. tetra-, pentapeptides) at a high and accurate level of theory. As a proof of the importance of the results mentioned before may serve that last year I was invited to present these results at the MIBIIII conference.
The expertise gained on this methodology has been very useful since I have been applying it subsequently in different projects. The first one concerns the study of: DNA Bases in Double-Stranded Octamers, Double-Stranded DNA Tetramer with a Ligand, The Core of the INK4 Tumor Supresor, Trp-Gly-Gly Tripeptide (Valdés et al. J. Phys. Chem. A 2007,111, 5642). The second project is about DNA base trimers (Valdés et al. Phys. Chem. Chem. Phys. 2007, 9, 5000) and finally, the third project is about non-standard base pairing and stacked structures in methyl xanthine clusters (Valdés et al. Phys. Chem. Chem. Phys. 2008, 10, 2819-2826).
Adittionally, I was also involved in a project in which a very new aspect in the ab initio calculations, the intramolecular BSSE and its influence in the calculation of relative energies of isolated systems, is explored (Valdés et al. J. Comp. Chem. 2008, 29, 861). I would like to stress here that this work, which I have presented at a seminar in Department of Physics and Astronomy of the University of Leeds, constitutes one of the very few studies on this topic published up to this date.
Concerning the theoretical study of isolated small peptides containing aromatic side chains by means of quantum chemical and molecular dynamic simulations, in the last year I have been also studying in detail the anharmonicity of these systems, the role played by the dispersion energy in their stability –which constitutes a pioneer work in the analysis of the nature of the intramolecular interaction by means of a quantum chemical methodology- as well as I have assessed the performance of the protocol of calculation that we have systematically employed for the study of isolated aromatic peptides by comparing the results obtained with the mentioned protocol with the results obtained by means of a newly developed methodology named metadynamics. The output of these studies is a paper recently published in Chem. Eur. J. 2008, 14, 4886.
Aiming to improve the computational efficacy of the quantum-chemical calculations on isolated aromatic peptides and specially thinking about their applicability to larger systems (tetra-,pentapeptides) we have assessed the performance of a broad range of methodologies, namely: (a) those standardly used and (b) newly developed methods and density functional theory functionals. As a result we have built up the first benchmark database on isolated aromatic small peptides that will help in future to assess the performance of new theoretical methods as well as to improve the parameterization of the empirical potentials used in molecular dynamic simulations (Valdés et al., Phys. Chem. Chem. Phys., 2008, 10, 2747-2757). This paper has been also published in the special issue of the journal dedicated to ‘stacking interactions’ as well as has been selected to be published in the Chemical Biology virtual Journal which collects the most relevant papers published in more than 15 different publications of the Royal Society of Chemistry (RSC) of the current year.
Finally, I would also like to remark from this period my third paper as corresponding author in which realistic model systems of aromatic-aromatic side chain interactions in proteins (in particular those π–π interactions occurring between adjacent residues along the protein sequence) are studied, has been published in the J. Chem. Theor. and Comput. 5, 2248-2256, 2009.