Institution: | aPrograma de Pós-Graduação em Química Orgânica, Instituto de Química, Universidade Federal Fluminense, Niterói, RJ, Brazil bDepartamento de Físico-Química, Instituto de Química, Universidade Federal Fluminense, Niterói, RJ, Brazil cDepartamento de Química Orgânica, Instituto de Química, Universidade Federal do Rio de Janeiro, Centro de Ciências Matemáticas e da Natureza, Rio de Janeiro, RJ, Brazil dDepartamento de Processos Orgânicos, Escola de Química, Universidade Federal do Rio de Janeiro, Centro de Tecnologia, Rio de Janeiro, RJ, Brazil eDepartment of Chemistry and Biochemistry, University of Oklahoma, Norman, OK, USA |
Abstract: | Conformational analysis of nucleosides may have direct applications to the structure–activity relationship (SAR) studies and in the design of new drug candidates. Although conformational analysis may be accessed in many different ways, in this work it was performed using molecular dynamics (MD) simulation in order to study the dynamic behavior of a nucleoside derivative of 1,4-dihydro-4-oxoquinoline-3-carboxylic acid, synthesized by our group as a potential antiviral agent. The MD simulation was carried out during 10 ns in vacuum and in a box of water at two different temperatures (i.e., 300 and 600 K) using the AMBER force field. The in vacuum MD simulation results are in agreement with the crystallographic structure and with the DFT calculations of the nucleoside, revealing the anti conformer as the more stable one. The simulation in water, however, shows that both conformers may exist at 300 K, the temperature of the in vivo and in vitro assays, revealing that both the syn and anti conformers should be considered in a MD simulation study of the inhibitor–enzyme complex. Simulations are also in agreement with the NOE experiment, which shows that the anti conformer is the preferential one in DMSO-d6 solution at 298 K. |