1 Department of Chemistry, Technical University of Denmark2 Organic Chemistry, Department of Chemistry, Technical University of Denmark3 UOS Pisa, Institute of Chemistry of Organometallic Compounds4 Pennsylvania State University5 Western University of Health Sciences, Department of Pharmaceutical Sciences6 Scuola Normale Superiore di Pisa7 Pennsylvania State University8 Scuola Normale Superiore di Pisa
In order to describe possible reaction mechanisms involving amino acids, and the evolution of the protonation state of amino acid side chains in solution, a reactive force field (ReaxFF-based description) for peptide and protein simulations has been developed as an expansion of the previously reported glycine parameters. This expansion consists of adding to the training set more than five hundred molecular systems, including all the amino acids and some short peptide structures, which have been investigated by means of quantum mechanical calculations. The performance of this ReaxFF protein force field on a relatively short time scale (500 ps) is validated by comparison with classical non-reactive simulations and experimental data of well characterized test cases, comprising capped amino acids, peptides, and small proteins, and reaction mechanisms connected to the pharmaceutical sector. A good agreement of ReaxFF predicted conformations and kinetics with reference data is obtained.
Physical Chemistry Chemical Physics, 2013, Vol 15, Issue 36, p. 15062-15077