title: PROTS: a fragment based protein thermo-stability potential.
abstract: Designing proteins with enhanced thermo-stability has been a main focus of protein engineering because of its theoretical and practical significance. Despite extensive studies in the past years, a general strategy for stabilizing proteins still remains elusive. Thus effective and robust computational algorithms for designing thermo-stable proteins are in critical demand. Here we report PROTS, a sequential and structural four-residue fragment based protein thermo-stability potential. PROTS is derived from a nonredundant representative collection of thousands of thermophilic and mesophilic protein structures and a large set of point mutations with experimentally determined changes of melting temperatures. To the best of our knowledge, PROTS is the first protein stability predictor based on integrated analysis and mining of these two types of data. Besides conventional cross validation and blind testing, we introduce hypothetical reverse mutations as a means of testing the robustness of protein thermo-stability predictors. In all tests, PROTS demonstrates the ability to reliably predict mutation induced thermo-stability changes as well as classify thermophilic and mesophilic proteins. In addition, this white-box predictor allows easy interpretation of the factors that influence mutation induced protein stability changes at the residue level.
authors: Applied Bioinformatics Laboratory, the University of Kansas, Lawrence, Kansas 66047, USA.
authors: Yunqi
authors: Y
authors: Li
authors: Jian
authors: J
authors: Zhang
authors: David
authors: D
authors: Tai
authors: C Russell
authors: CR
authors: Middaugh
authors: Yang
authors: Y
authors: Zhang
authors: Jianwen
authors: J
authors: Fang
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry; D002645:Chickens; D003198:Computer Simulation; D016220:Fibroblast Growth Factor 1 / Q000737:chemistry; D006801:Humans; D016014:Linear Models; D008958:Models, Molecular; D009113:Muramidase / Q000737:chemistry; D020125:Mutation, Missense; D015202:Protein Engineering; D055550:Protein Stability; D017433:Protein Structure, Secondary; D012372:ROC Curve; D012984:Software; D013816:Thermodynamics; D044366:Transition Temperature
chemical_list: D001426:Bacterial Proteins; C018150:subtilisin inhibitor protein, Streptomyces; D016220:Fibroblast Growth Factor 1; D009113:Muramidase