An Effective Cumulative Torsion Angles Model for Prediction of Protein Folding Rates

Abstract

Background: Protein folding rate is mainly determined by the size of the conformational space to search, which in turn is dictated by factors such as size, structure and amino-acid sequence in a protein. It is important to integrate these factors effectively to form a more precisely description of conformation space. But there is no general paradigm to answer this question except some intuitions and empirical rules. Therefore, at the present stage, predictions of the folding rate can be improved through finding new factors, and some insights are given to the above question. Objective: Its purpose is to propose a new parameter that can describe the size of the conformational space to improve the prediction accuracy of protein folding rate. Method: Based on the optimal set of amino acids in a protein, an effective cumulative backbone torsion angles (CBTAeff) was proposed to describe the size of the conformational space. Linear regression model was used to predict protein folding rate with CBTAeff as a parameter. The degree of correlation was described by the coefficient of determination and the mean absolute error MAE between the predicted folding rates and experimental observations. Results: It achieved a high correlation (with the coefficient of determination of 0.70 and MAE of 1.88) between the logarithm of folding rates and the (CBTAeff)0.5 with experimental over 112 twoand multi-state folding proteins. Conclusion: The remarkable performance of our simplistic model demonstrates that CBTA based on optimal set was the major determinants of the conformation space of natural proteins.

In Silico and In Vitro Analysis of Major Cannabis-Derived Compounds as Fatty Acid Amide Hydrolase Inhibitors

“…In this context, it should be noted that torsion angles are among the most important local structural parameters that drive protein folding [64]. Ramachandran plot analysis of such torsion angles showed that the two MODELLER structures had a higher percentage of residues (90.8% and 91.8%, respectively) in favorable regions [65].…”

Topological principles of protein folding

“…For such proteins, the folding pathway may be characterized by kinetic traps and escape from low free energy conformations. 4,5 In more recent years, other models have been suggested for folding rate prediction, based on total contact distance, 6 a small selection of contact information, 7 cumulative torsion angle 8 and other structural information. [9][10][11][12][13] Moreover, an evolution of the concept of contact order called partial contact order was envisioned in order to follow the progression of such topological descriptors from the unfolded to the folded state.…”