ModFOLD8: accurate global and local quality estimates for 3D protein models

Abstract

Methods for estimating the quality of 3D models of proteins are vital tools for driving the acceptance and utility of predicted tertiary structures by the wider bioscience community. Here we describe the significant major updates to ModFOLD, which has maintained its position as a leading server for the prediction of global and local quality of 3D protein models, over the past decade (>20 000 unique external users). ModFOLD8 is the latest version of the server, which combines the strengths of multiple pure-single and quasi-single model methods. Improvements have been made to the web server interface and there has been successive increases in prediction accuracy, which were achieved through integration of newly developed scoring methods and advanced deep learning-based residue contact predictions. Each version of the ModFOLD server has been independently blind tested in the biennial CASP experiments, as well as being continuously evaluated via the CAMEO project. In CASP13 and CASP14, the ModFOLD7 and ModFOLD8 variants ranked among the top 10 quality estimation methods according to almost every official analysis. Prior to CASP14, ModFOLD8 was also applied for the evaluation of SARS-CoV-2 protein models as part of CASP Commons 2020 initiative. The ModFOLD8 server is freely available at: https://www.reading.ac.uk/bioinf/ModFOLD/.

Molecular Analysis of Streptomycin Resistance Genes in Clinical Strains of Mycobacterium tuberculosis and Biocomputational Analysis of the MtGidB L101F Variant

“…C-score was used to measure the modeling confidence [53,54]. The top-ranked 3D structure was improved using ReFOLD (http: //www.reading.ac.uk/bioinf/ReFOLD/, accessed on 10 November 2020), a computational tool for model refinement guided by accurate quality estimates [55,56], and the structural precision was estimated using ModFold (https://www.reading.ac.uk/bioinf/ModFOLD/, accessed on 20 November 2020), a server for global and local quality assessment [57]. The 3D model was further analyzed using Procheck's Ramachandran plot [58] and ProSA's Z-score plot [59,60].…”

Gene Analysis, Cloning, and Heterologous Expression of Protease from a Micromycete Aspergillus ochraceus Capable of Activating Protein C of Blood Plasma

“…The tertiary structure prediction was made with AlphaFold 2.0 [ 16 ] with default settings and visualised with PyMOL v.2 [ 17 ]. The model quality assessment was performed with ProQ3D server ( accessed on 20 May 2021) [ 18 ] and ModFOLD8 server ( accessed on 25 May 2021) [ 19 ]. The predicted structure was superimposed with the HHpred highest-score fungal protease from Lecanicillium psalliotae sequence (PDB ID: 3F7M) using the functionality of PyMOL.…”

Curtobacterium spp. and Curtobacterium flaccumfaciens: Phylogeny, Genomics-Based Taxonomy, Pathogenicity, and Diagnostics

“…First, the structure was predicted using AlphaFold 2.0 [45] with default settings, I-TASSER [46,47] with default settings, Phyre2 [32] in intensive modelling mode and Rosetta [48] using RoseTTAFold modelling mode [49]. The accuracy of prediction of the best-scoring models obtained by the methods listed above was estimated using ModFold8 [50], and the model with the highest global model quality score was used for the refinement of the structure using ReFOLD3 [51] in the next step. The quality of the prediction of the resulting structure was also estimated by ModFold8 [50].…”

“…The accuracy of prediction of the best-scoring models obtained by the methods listed above was estimated using ModFold8 [50], and the model with the highest global model quality score was used for the refinement of the structure using ReFOLD3 [51] in the next step. The quality of the prediction of the resulting structure was also estimated by ModFold8 [50]. Similar experimentally obtained structures were found by the HHpred [31], Phyre2 [32] and I-TASSER [47] servers.…”