title: Prediction of protein motions from amino acid sequence and its application to protein-protein interaction.
abstract: BACKGROUND
  Structural flexibility is an important characteristic of proteins because it is often associated with their function. The movement of a polypeptide segment in a protein can be broken down into two types of motions: internal and external ones. The former is deformation of the segment itself, but the latter involves only rotational and translational motions as a rigid body. Normal Model Analysis (NMA) can derive these two motions, but its application remains limited because it necessitates the gathering of complete structural information.
  
  
  RESULTS
  In this work, we present a novel method for predicting two kinds of protein motions in ordered structures. The prediction uses only information from the amino acid sequence. We prepared a dataset of the internal and external motions of segments in many proteins by application of NMA. Subsequently, we analyzed the relation between thermal motion assessed from X-ray crystallographic B-factor and internal/external motions calculated by NMA. Results show that attributes of amino acids related to the internal motion have different features from those related to the B-factors, although those related to the external motion are correlated strongly with the B-factors. Next, we developed a method to predict internal and external motions from amino acid sequences based on the Random Forest algorithm. The proposed method uses information associated with adjacent amino acid residues and secondary structures predicted from the amino acid sequence. The proposed method exhibited moderate correlation between predicted internal and external motions with those calculated by NMA. It has the highest prediction accuracy compared to a naïve model and three published predictors.
  
  
  CONCLUSIONS
  Finally, we applied the proposed method predicting the internal motion to a set of 20 proteins that undergo large conformational change upon protein-protein interaction. Results show significant overlaps between the predicted high internal motion regions and the observed conformational change regions.
authors.affiliation: Computational Biology Research Center (CBRC), National Institute of Advanced Industrial Science and Technology (AIST),2-42, Aomi, Koto-ku, Tokyo, 135-0064, Japan. hirose-shuichi@aist.go.jp
authors.forename: Shuichi
authors.initials: S
authors.lastname: Hirose
authors.forename: Kiyonobu
authors.initials: K
authors.lastname: Yokota
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kuroda
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Wako
authors.forename: Shigeru
authors.initials: S
authors.lastname: Endo
authors.forename: Satoru
authors.initials: S
authors.lastname: Kanai
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Noguchi
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D019295:Computational Biology; D006801:Humans; D008958:Models, Molecular; D009068:Movement; D011485:Protein Binding; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*; D013696:Temperature
chemical_list: D011506:Proteins