biostudies-literatureUnknown27Sicheri EThe projection of conservation onto the surface of a protein's 3D structure is a powerful way of inferring functionally important regions. For this reason, we created ProteoSync, a Python program that semi-automates the process. The program creates an annotated sequence alignment of orthologs from a diverse set of selectable species and enables the fast projection of amino acid conservation onto a predicted or known 3D model in PyMOL ¹. As a test case, we used ProteoSync to analyze a subset of 31 F-box proteins, which function as substrate recognition subunits for a large family of Cul1-based E3 ubiquitin ligases. We correctly identified known substrate interaction surfaces for 11 F-box members with previously solved structures. We also identified likely ligand binding sites forComputational and structural biotechnology journal4026-4039https://www.ebi.ac.uk/biostudies/studies/S-EPMC12475580biostudies-literatureAnalysis of Fbox substrate adapter proteins using <i>ProteoSync</i>, a program for projection of evolutionary conservation onto protein atomic coordinates.PMC12475580Tyers MMao DSicheri ESicheri FfalseAnalysis of Fbox substrate adapter proteins using <i>ProteoSync</i>, a program for projection of evolutionary conservation onto protein atomic coordinates.The projection of conservation onto the surface of a protein's 3D structure is a powerful way of inferring functionally important regions. For this reason, we created ProteoSync, a Python program that semi-automates the process. The program creates an annotated sequence alignment of orthologs from a diverse set of selectable species and enables the fast projection of amino acid conservation onto a predicted or known 3D model in PyMOL ¹. As a test case, we used ProteoSync to analyze a subset of 31 F-box proteins, which function as substrate recognition subunits for a large family of Cul1-based E3 ubiquitin ligases. We correctly identified known substrate interaction surfaces for 11 F-box members with previously solved structures. We also identified likely ligand binding sites for2025-01-01T00:00:00Z20252026-06-03T23:51:36.943Z2026-05-03T03:11:16.107ZS-EPMC124755804101782710.1016/j.csbj.2025.09.012