Entropy, Fluctuations, and Disordered Proteins

Entropy

Andrzej Kloczkowski¹  A.Keith Dunker²  Eshel Faraggi³  RobertL. Jernigan⁴ 

[1] Battelle Center for Mathematical Medicine, The Research Institute at Nationwide Children’s Hospital, Columbus, OH 43205, USA;Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA;Department of Physics, Indiana University Purdue University Indianapolis, Indianapolis, IN 46202, USA;Roy J. Carver Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, IA 50011, USA;

关键词: protein disorder;    protein structure;    entropy;    fluctuations;    mutations;   

DOI  :  10.3390/e21080764

来源: DOAJ

【 摘 要 】

Entropy should directly reflect the extent of disorder in proteins. By clustering structurally related proteins and studying the multiple-sequence-alignment of the sequences of these clusters, we were able to link between sequence, structure, and disorder information. We introduced several parameters as measures of fluctuations at a given MSA site and used these as representative of the sequence and structure entropy at that site. In general, we found a tendency for negative correlations between disorder and structure, and significant positive correlations between disorder and the fluctuations in the system. We also found evidence for residue-type conservation for those residues proximate to potentially disordered sites. Mutation at the disorder site itself appear to be allowed. In addition, we found positive correlation for disorder and accessible surface area, validating that disordered residues occur in exposed regions of proteins. Finally, we also found that fluctuations in the dihedral angles at the original mutated residue and disorder are positively correlated while dihedral angle fluctuations in spatially proximal residues are negatively correlated with disorder. Our results seem to indicate permissible variability in the disordered site, but greater rigidity in the parts of the protein with which the disordered site interacts. This is another indication that disordered residues are involved in protein function.

【 授权许可】

Unknown