Free Energy Estimates of All-Atom Protein Structures Using Generalized Belief Propagation

We present a technique for approximating the free energy of protein structures using Generalized Belief Propagation (GBP). The accuracy and utility of these estimates are then demonstrated in two different application domains. First, we show that the entropy component of our free energy estimates can useful in distinguishing native protein structures from decoys -- structures with similar internal energy to that of the native structure, but otherwise incorrect. Our method is able to correctly identify the native fold from among a set of decoys with 87.5% accuracy over a total of 48 different immunoglobin folds. The remaining 12.5% of native structures are ranked among the top 4 of all structures. Second, we show that our estimates of G upon mutation upon mutation for three different data sets have linear correlations between 0.63-0.70 with experimental values and statistically significant p-values. Together, these results suggests that GBP is an effective means for computing free energ...

• Type: Conference
• Year: 2007
• Where: RECOMB
• Authors: Hetunandan Kamisetty, Eric P. Xing, Christopher James Langmead
• Keywords: Computational Biology, Free Energy, Molecular Dynamic Simulations, Probabilistic Graphical Models, RECOMB 2007