Balasubramanian Hariha and Samuel Selvaraj Pages 143 - 151 ( 9 )
Free energy of unfolding (ΔGu) is the difference between the free energy values of the folded and unfolded structures of a protein. A successful model describing both folding/unfolding rates of proteins should be able to provide considerable insight on free energy of unfolding. In our earlier works, we have shown that Long-range Order (LRO) correlates well with both folding/unfolding rates of two-state proteins. In the present work, we examine the extent to which LRO can be used to predict the free energy of unfolding. For a standard data set of 29 two-state proteins, no significant correlation was observed between ΔGu and LRO. However after grouping the proteins according to their structural class, all-alpha and all-beta proteins showed a better correlation of r = 0.77 and r = 0.89, whereas mixed-class proteins still showed a poor correlation. We have also analyzed the relationship between various other structure derived topological parameters with ΔGu values and the results observed showed that all these parameters also gave a poor correlation with ΔGu values when structural classification was not taken into account. Similar to LRO, after structural classification better improvement in correlation was observed for all-alpha and all-beta proteins and not a single topological parameter showed reasonable correlation with ΔGu values of mixed-class proteins and suggested that understanding ΔGu values of mixed-class proteins remains complicated. Our present work implies that theoretical models to understand stability of proteins can be developed based on their 3-D structures and further experimental/theoretical studies will shed light on these predictions.
Long range contacts, long-range order, sequence separation, spatial distance, structural class, Free energy of unfolding, hydrophobic interactions, hydrogen bonds, heat capacity, entropy
Department of Bioinformatics, School of Life Sciences, Bharathidasan University, Tiruchirappalli 620 024, Tamil Nadu, India.