ProteinLIPs is an online server for proteomic analysis developed by Helena García-Cebollada, Alfonso López, Vladimir Espinosa-Angarica, Juan José Galano-Frutos and Javier Sancho at the Department of Biochemistry and Molecular and Cell Biology of the University of Zaragoza, Spain. ProteinLIPs identifies, in proteins, highly polar and poorly packed buried interfaces (LIP: Light Interface of high Polarity), which may constitute preferential locus for protein stabilization design in non-two-state proteins. On the other hand, LIPs being weak regions of folded proteins, they may play relevant roles in protein dynamics.
The algorithm for calculating protein LIPs is based on a per-residue estimation of two physical parameters of buried interfaces in a queried protein: the polarity ratio (PRinter) and the packing density (ρinter). These two parameters are iteratively computed using a sequence probe of eight contiguous residues and the calculated values are assigned to the fourth residue of the sequence. When the scanning of the protein chain is completed, a dual sequence profile (PRinter at the top and ρinter at the bottom) is built, from which the main faces (mLIP) of all the LIPs present in the protein are calculated by applying rigorously defined cutoffs. The second face of each LIP, composed by non-contiguous residues and termed cLIP, is also calculated according to burial by its corresponding mLIP. For each LIP, the two faces are shown on the protein 3D-structure through an interactive JSmol visualization panel.
ProteinLIPs can analyze both protein monomers and oligomers, calculating separately the mLIPs of each monomer (intra mLIPs) as well as mLIPs located at monomer-monomer interfaces (inter mLIPs). For trimers or larger oligomers, users can specify the pair of monomers in contact for which they wish to determine the LIPs.
The ProteinLIPs server performs automated 3D-structure analysis of PDB files. Upon a PDB ID query by the user, the server connects with the PISA server or, if the structure is not found there, with the Protein Data Bank API in order to download the PDB file of the protein biological unit. Alternatively, a PDB-formatted protein structure file can be uploaded by the user. ProteinLIPs requires users to provide an e-mail address.
Once the calculation is complete, the results are visualized on the same browser tab where the user initiated the calculation request. Simultaneously, a link is sent via e-mail to the user allowing the user to visualize the results on the web. On the results screen, a button enables the download of a compressed ZIP file containing the calculated sequence profiles in PNG format, the PDB structure file used for the calculation, and a summary of the results. The summary includes the spans of the calculated intra mLIPs and of inter mLIPs (for oligomers), the interacting residues in the corresponding cLIPs, as well as information on any structural or sequence gap found in the queried PDB.
The integrated Java Script molecular viewer JSmol enables the representation of the mLIPs on the 3D-structure of the queried protein, along with their interacting cLIPs. Expandable sequence bars (RCSB Saguaro 1D Feature Viewer) located below the JSmol panel facilitate individual and multiple selection/visualization of the identified LIPs. The highlighted mLIPs in the bars work as on/off buttons, allowing them to be easily displayed or hidden on the protein 3D-structure (JSmol panel).
Gaps found in an analysed protein structure (non-solved residues) will appear as unconnected regions in the LIPs profiles, whereas gaps present in the sequence numbering will appear in the LIPs profiles as discontinuous lines (indicated in the legend). The ProteinLIPs server retains the residue numbering from the original PDB file.
ProteinLIPs 2.0 © 2025 Javier Sancho's Lab. All Rights Reserved.