Cryptic intermediates and metastable states of proteins as predicted by OneG computational method

Abstract

Understanding structural excursions of proteins under folding conditions is crucial to map energy landscapes of proteins. In the present study, OneG computational tool has been used for analyzing possible existence of cryptic intermediates and metastable states of 26 proteins for which three prerequisite inputs of the OneG such as atomic coordinates of proteins, free energy of unfolding (ΔG_U) and free energy of exchange (ΔG_HX) determined in the absence of denaturant were available during the course of the study. The veraciousness of the tool on predicting the partially folded states of the proteins has been comprehensively described using experimental data available for 15 of the 26 proteins. Meanwhile, possible existence of partially structured states in the folding pathways of 11 other proteins has also been delineated as predicted by the OneG. In addition to mapping the folding pathways of proteins, the salient merits of the tool on systematically addressing the discrepancy between the ΔG_U and the ΔG_HX of the proteins have also been dealt.

Communicated by Ramaswamy H. Sarma

Keywords:

• Cryptic intermediates
• free energy
• metastable states
• native folding
• OneG

Acknowledgements

The author would like to acknowledge the KAHE research grant (KAHE/R-Acad/A1/Seedmoney/8970/2019/) and the DST research grant (SR/FIST/LS-1/2018/187) for the timely scientific supports towards the research works.

Disclosure statement

The authors declare that there are no conflicts of interest in the manuscript.

Authors contributions

TR collected the data. TS wrote the manuscript, which was revised by both the authors.