The virtual screening of synthetic proteins is to develop an effective method to predict and screen out
synthetic proteins that are similar to the target sequences in terms of their structural and
physicochemical properties by combining advanced computational tools and models, such as
AlphaFold2 and ESM2. Through virtual screening, the experimental cost and time period can be
reduced, and some guidelines for customized design of new proteins can be provided. All similar
research efforts have promoted the advancement in the fields of synthetic biology and biomedical
science. In this paper, we first calculate the backbone distances between synthetic proteins and target
sequences using the AlphaFold2 tool to ensure that they are structurally similar. Secondly, based on the
ESM2 model, the concept of feature distance is proposed to ensure that the two proteins are consistent
in physicochemical properties. In the experiments, the steps of virtual screening of synthetic proteins
are summarized, and the synthetic proteins are arranged in ascending order by backbone distance and
feature distance. If the same synthetic protein appears in the first position of the two sorted tables, then
select that protein. If different synthetic proteins appear in the first position of the two sorted tables,
the synthetic protein with higher solubility will be selected. Repeat this process for other ranking
positions. The experimental results show that this process derived from backbone distance and feature
distance is a necessary and useful tool to select preferred synthetic proteins before entering the lab
experimental session.