The Vajda lab, in collaboration with the Kozakov lab at Stony Brook University, recently added two new servers that use template-based methods for predicting the structure of complexes. ClusPro TBM employs homology modeling tools to build models of protein complexes based on similar complex structures. In contrast to the ClusPro server, ClusPro TBM thus can use sequences rather than structures of component proteins as input. Although the server, freely available for non-commercial use at https://tbm.cluspro.org, has performed well in CASP13 (1, 2), it should be still considered as a beta version. In fact, we continuously test different strategies, e.g., the selection and combination of templates, generating multiple models, and the use of various scoring functions, in order to better understand the factors affecting prediction accuracy and to improve performance.
The second server, ClusPro LigTBM (3), performs template-based docking of small ligands to proteins. It allows the user to specify the target protein as a PDB file and the ligand as a SMILES string. The server will then automatically search for templates and use them for docking, presenting the user with top-scoring poses and their confidence scores. The server is based on the method developed by the Kozakov lab, which was one of the best performers in the last round of the D3R (Drug Design Data Resource) Grand Challenge. The server is publicly available as part of the ClusPro docking server suite at https://ligtbm.cluspro.org/. As in the case of ClusPro TBM, we plan substantial improvements in the technology by adding more advanced protein modeling and scoring functions, the targets of ongoing work in our lab.
User inputs for ClusPro TBM (left) and ClusPro ligTBM (right).
Since the algorithms used in both servers are under development and the servers are being extensively tested, we appreciate comments and suggestions from users.
K. A. Porter et al., Template-based modeling by ClusPro in CASP13 and the potential for using co-evolutionary information in docking. Proteins 87, 1241-1248 (2019).
D. Padhorny et al., ClusPro in rounds 38 to 45 of CAPRI: Toward combining template-based methods with free docking. Proteins 10.1002/prot.25887 (2020).
A. Alekseenko et al., ClusPro LigTBM: Automated Template-based Small Molecule Docking. J Mol Biol 10.1016/j.jmb.2019.12.011 (2019).