OPUS-Rota2: An Improved Fast and Accurate Side-Chain Modeling Method

Abstract

Side-chain modeling plays a critical role in protein structure prediction. However, in many current methods, balancing the speed and accuracy is still challenging. In this paper, on the basis of our previous work OPUS-Rota (Protein Sci. 2008, 17, 1576–1585), we introduce a new side-chain modeling method, OPUS-Rota2, which is tested on both a 65-protein test set (DB65) in the OPUS-Rota paper and a 379-protein test set (DB379) in the SCWRL4 paper. If the main chain is native, OPUS-Rota2 is more accurate than OPUS-Rota, SCWRL4, and OSCAR-star but slightly less accurate than OSCAR-o. Also, if the main chain is non-native, OPUS-Rota2 is more accurate than any other method. Moreover, OPUS-Rota2 is significantly faster than any other method, in particular, 2 orders of magnitude faster than OSCAR-o. Thus, the combination of higher accuracy and speed of OPUS-Rota2 in modeling side chains on both the native and non-native main chains makes OPUS-Rota2 a very useful tool in protein structure modeling.

Recent Applications of Deep Learning Methods on Evolution- and Contact-Based Protein Structure Prediction

“…The homology modeling is generally performed by the following steps: (i) identify and select the eligible templates, i.e., other homologous proteins with known 3D structures (related programs: BLAST, PSI-BLAST, HH-suite (HHsearch, HHblits, and HHPred), and JackHMMer, among others); (ii) multiple sequence alignment (related programs: CLUSTAL Omega, MUSCLE, and so on) [ 91 , 92 ]; (iii) 3D model building (related programs: SWISS-MODEL, MODELLER, I-TASSER, and so on) [ 93 , 94 , 95 ]; (iv) modeling of loops that are variable and not conserved region; (v) side-chain modeling based on rotamer library, a scoring function, and a scanning method (related programs: OPUS-Rota2, FASPR, SCWRL) [ 96 , 97 , 98 ]; (vi) model optimization increasing the quality of the final model (generally energy minimization, molecular dynamics, or Monte Carlo simulations); and (vii) model evaluation and validation.…”

OPUS-Rota4: a gradient-based protein side-chain modeling framework assisted by deep learning-based predictors

“…Protein side-chain modeling is an important task since the side-chain conformations are closely relevant to their biological functions [ 1 , 2 ]. In recent years, many successful programs have been proposed to address the side-chain modeling problem [ 1–11 ].…”

“…Many traditional protein side-chain modeling programs [ 1 , 2 , 5 , 6 ] are composed of three key components: a rotamer library, an energy function and a search method. One of the advantages of these methods is that they are very fast.…”

OPUS-Rota4: A Gradient-Based Protein Side-Chain Modeling Framework Assisted by Deep Learning-Based Predictors

“…The traditional protein side-chain modeling programs 1,4,5,10 are composed of three key components: a rotamer library, an energy function, and a search method.…”

“…Protein side-chain modeling is an important task since the uniqueness of protein structure is largely determined by the packing of its side-chain conformation 1 . In recent years, many successful programs have been proposed to address this issue [1][2][3][4][5][6][7][8][9][10][11] .…”