In silico evaluation of cross linking effects on denaturant meq values and delta Cp upon protein unfolding

ABSTRACT

Important thermodynamic parameters including denaturant equilibrium m values [meq] and heat capacity changes [delta Cp] can be predicted based on changes in Solvent Accessible Surface Area [SASA] upon unfolding. Cross links such as disulfide bonds influence the stability of the proteins by decreasing the entropy gain as well as reduction of SASA of unfolded state. The aim of the study was to develop mathematical models to predict the effect of cross links on delta SASA and ultimately on meq and delta Cp based on in silico methods. Changes of SASA upon computationally simulated unfolding were calculated for a set of 45 proteins with known meq and delta Cp values and the effect of cross links on delta SASA of unfolding was investigated. The results were used to predict the meq of denaturation for guanidine hydrochloride and urea, as well as delta Cp for the studied proteins with overall error of 20%, 31% and 17%, respectively. The results of the current study were in close agreement with those obtained from the previous studies