1 A Probabilistic Method to Correlate Ion-pairs to Protein Thermostability Shir-Ly Huang 1,* , Li-Cheng Wu 2 , Hsien-Da Huang 3 , Han-Kuen Liang 4 , Ming-Tat Ko 4 , and Jorng-Tzong Horng 1, 2 1 Department of Life Science, National Central University, Taiwan 2 Department of Computer Science and Information Engineering, National Central University, Taiwan 3 Department of Biological Science and Technology, Institute of Bioinformatics, National Chiao-Tung University, Taiwan 4 Institute of Information Science, Academia Sinica, Taiwan *E-mail: slhuang@cc.ncu.edu.tw Abstract: Recent developments in research on the stability of proteins show that ion-pairs potentially contribute to the thermostability of proteins, according to comparisons of ion-pairs between homologous structures. This study proposes a probabilistic Bayesian statistical method to predict efficiently the thermostability of proteins based on considering the properties of ion-pairs. The experimental results suggest that the number, types, and bond distance of ion-pairs can be used to predict thermostability of proteins with functions similar to each other with a high accuracy up to 80%. The predictions have high precision of 99%, especially for hyperthermophilic proteins. The experimental results of proteins with different functions also indicate that the number of ion-pairs is related to the thermostability of proteins, and predictions of thermostability can also be made for proteins with different functions. Keywords: Ion-Pairs, Protein Thermostability, Bayesian Introduction Proteins are the end-products of most gene expressions. Some of these proteins are used widely in industry as biocatalysts (Burton 2003). Chemical reactions often need to be performed at high temperatures to accelerate industrial processes. However, not many enzymes are stable when heated * Correspondence: Shir-Ly Huang E-mail: slhuang@cc.ncu.edu.tw Department of Life Science, National Central University, No. 300, Jungda Rd., Jhongli City, Taoyuan, Taiwan 320, R. O. C.