ProFitFun: A Protein Tertiary Structure Fitness Function for Quantifying the Accuracies of Model Structures.

MOTIVATION An accurate estimation of the quality of protein model structures typifies as a cornerstone in protein structure prediction regimes. Despite the recent groundbreaking success in the field of protein structure prediction, there are certain prospects for the improvement in model quality estimation at multiple stages of protein structure prediction and thus, to further push the prediction accuracy. Here, a novel approach, named ProFitFun, for assessing the quality of protein models is proposed by harnessing the sequence and structural features of experimental protein structures in terms of the preferences of backbone dihedral angles and relative surface accessibility of their amino acid residues at the tripeptide level. The proposed approach leverages upon the backbone dihedral angle and surface accessibility preferences of the residues by accounting for its N-terminal and C-terminal neighbors in the protein structure. These preferences are employed to evaluate protein structures through a machine learning approach and tested on an extensive dataset of diverse proteins. RESULTS The approach was extensively validated on a large test dataset (n = 25,005) of protein structures, comprising 23,661 models of 82 non-homologous proteins and 1,344 non-homologous experimental structures. Additionally, an external dataset of 40,000 models of 200 non-homologous proteins was also used for the validation of the proposed method. Both datasets were further employed for benchmarking the proposed method with four different state-of-the-art methods for protein structure quality assessment. In the benchmarking, the proposed method outperformed some state of the art methods in terms of Spearman's and Pearson's correlation coefficients, average GDT-TS loss, sum of z-scores, and average absolute difference of predictions over corresponding observed values. The high accuracy of the proposed approach promises a potential use of the sequence and structural features in computational protein design. AVAILABILITY http://github.com/KYZ-LSB/ProTerS-FitFun. SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.