The present invention relates to granulocyte colony stimulating factor ("G-CSF") polypeptide analog compositions. The concept detailed herein provides methods for screening G-CSF analogs, designed with one or more substitutions to amino acids, and selecting analogs for use as G-CSF replacements or antagonists, and may be generalizable beyond G-CSF analogs as well. In addition, pharmaceutical compositions and methods of use are provided for analogs so selected.