%0 Journal Article
%T Free Energy Profile of APOBEC3G Protein Calculated by a Molecular Dynamics Simulation
%A Yoshifumi Fukunishi
%A Saki Hongo
%A Masami Lintuluoto
%A Hiroshi Matsuo
%J Biology
%D 2012
%I MDPI AG
%R 10.3390/biology1020245
%X The human APOBEC3G protein (A3G) is a single-stranded DNA deaminase that inhibits the replication of retrotransposons and retroviruses, including HIV-1. Atomic details of A3G¡¯s catalytic mechanism have started to emerge, as the structure of its catalytic domain (A3Gctd) has been revealed by NMR and X-ray crystallography. The NMR and crystal structures are similar overall; however, differences are apparent for ¦Â2 strand (¦Â2) and loops close to the catalytic site. To add some insight into these differences and to better characterize A3Gctd dynamics, we calculated its free energy profile by using the Generalized-Born surface area (GBSA) method accompanied with a molecular dynamics simulation. The GBSA method yielded an enthalpy term for A3Gctd¡¯s free energy, and we developed a new method that takes into account the distribution of the protein¡¯s dihedral angles to calculate its entropy term. The structure solved by NMR was found to have a lower energy than that of the crystal structure, suggesting that this conformation is dominant in solution. In addition, ¦Â2-loop-¦Â2¡¯ configuration was stable throughout a 20-ns molecular dynamics (MD) simulation. This finding suggests that in solution A3Gctd is not likely to adopt the continuous ¦Â2 strand configuration present in the APOBEC2 crystal structure. In the NMR structure, the solvent water accessibility of the catalytic Zn 2+ was limited throughout the 20-ns MD simulation. This result explains previous observations in which A3G did not bind or catalyze single cytosine nucleotide, even when at excessive concentrations.
%K APOBEC3G
%K GBSA
%K molecular dynamics simulation
%K free energy surface
%K protein structure
%K NMR
%K HIV-1
%U http://www.mdpi.com/2079-7737/1/2/245