Species specificity of the complement inhibitor compstatin investigated by all-atom molecular dynamics simulations.

ABSTRACT: The development of compounds to regulate the activation of the complement system in non-primate species is of profound interest because it can provide models for human diseases. The peptide compstatin inhibits protein C3 in primate mammals and is a potential therapeutic agent against unregulated activation of complement in humans but is inactive against nonprimate species. Here, we elucidate this species specificity of compstatin by molecular dynamics simulations of complexes between the most potent natural compstatin analog and human or rat C3. The results are compared against an experimental conformation of the human complex, determined recently by X-ray diffraction at 2.4-A resolution. The human complex simulations provide information on the relative contributions to stability of specif

SUBMITTER: Tamamis P 

PROVIDER: S-EPMC3138065 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature