Improvement of the relative entropy based protein folding method

The “relative entropy” has been used as a minimization function to predict the tertiary structure of a protein backbone, and good results have been obtained. However, in our previous work, the ensemble average of the contact potential was estimated by an approximate calculation. In order to improve the theoretical integrity of the relative-entropy-based method, a new theoretical calculation method of the ensemble average of the contact potential was presented in this work, which is based on the thermodynamic perturbation theory. Tests of the improved algorithm were performed on twelve small proteins. The root mean square deviations of the predicted versus the native structures from Protein Data Bank range from 0.40 to 0.60 nm. Compared with the previous approximate values, the average prediction accuracy is improved by 0.04 nm. Contributed equally to this work Supported by the National Natural Science Foundation of China (Grant No. 30670497), the Beijing Natural Science Foundation (Grant No. 5072002), and the Specialized Research Foundation for the Doctoral Program of Higher Education (Grant No. 200800050003)