Open Access Highly Accessed Research article

Prediction of protein motions from amino acid sequence and its application to protein-protein interaction

Shuichi Hirose12*, Kiyonobu Yokota1, Yutaka Kuroda3, Hiroshi Wako24, Shigeru Endo5, Satoru Kanai6 and Tamotsu Noguchi12

Author Affiliations

1 Computational Biology Research Center (CBRC), National Institute of Advanced Industrial Science and Technology (AIST),2-42, Aomi, Koto-ku, Tokyo, 135-0064, Japan

2 Research Institute of IT Biology/Faculty of Science and Engineering, Waseda University,2-42, Aomi, Koto-ku, Tokyo, 135-0064, Japan

3 Department of Biotechnology and Life Science, Graduate School of Engineering, Tokyo University of Agriculture and Technology,12-24-16, Naka-machi, Koganei-shi, Tokyo, 184-8588, Japan

4 School of Social Sciences, Waseda University,1-6-1, Nishi-Waseda, Shinjuku-ku, Tokyo, 169-8050, Japan

5 Department of Physics, School of Science, Kitasato University,1-15-1, Kitasato, Sagamihara, 228-8555, Japan

6 PharmaDesign, Inc.,2-19-8, Hatchobori, Chuo-ku, Tokyo, 104-0032, Japan

For all author emails, please log on.

BMC Structural Biology 2010, 10:20  doi:10.1186/1472-6807-10-20

Published: 13 July 2010



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.


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.


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.