Normal mode analysis as a method to derive protein dynamics information from the Protein Data Bank
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Normal mode analysis (NMA) can facilitate quick and systematic investigation of protein dynamics using data from the Protein Data Bank (PDB). We developed an elastic network model-based NMA program using dihedral angles as independent variables. Compared to the NMA programs that use Cartesian coordinates as independent variables, key attributes of the proposed program are as follows: (1) chain connectivity related to the folding pattern of a polypeptide chain is naturally embedded in the model; (2) the full-atom system is acceptable, and owing to a considerably smaller number of independent variables, the PDB data can be used without further manipulation; (3) the number of variables can be easily reduced by some of the rotatable dihedral angles; (4) the PDB data for any molecule besides proteins can be considered without coarse-graining; and (5) individual motions of constituent subunits and ligand molecules can be easily decomposed into external and internal motions to examine their mutual and intrinsic motions. Its performance is illustrated with an example of a DNA-binding allosteric protein, a catabolite activator protein. In particular, the focus is on the conformational change upon cAMP and DNA binding, and on the communication between their binding sites remotely located from each other. In this illustration, NMA creates a vivid picture of the protein dynamics at various levels of the structures, i.e., atoms, residues, secondary structures, domains, subunits, and the complete system, including DNA and cAMP. Comparative studies of the specific protein in different states, e.g., apo- and holo-conformations, and free and complexed configurations, provide useful information for studying structurally and functionally important aspects of the protein.
KeywordsElastic network model Protein structure network Catabolite activator protein Full-atom system Decomposition into internal and external motions
This work was supported by a JSPS Grant-in-Aid for Scientific Research (C) (grant no. 16K00407).
Compliance with ethical standards
Conflict of interest
Hiroshi Wako declares that he has no conflict of interest. Shigeru Endo declares that he has no conflict of interest.
This article does not contain any studies with human participants or animals performed by any of the authors.
- Hinsen K (1998) Analysis of domain motions by approximate normal mode calculations. Proteins 33:417–429. https://doi.org/10.1002/(SICI)1097-0134(19981115)33:3<417::AID-PROT10>3.0.CO;2-8 CrossRefPubMedGoogle Scholar
- Ishida H, Jochi Y, Kidera A (1998) Dynamic structure of subtilisin-eglin c complex studied by normal mode analysis. Proteins 32:324–333. https://doi.org/10.1002/(SICI)1097-0134(19980815)32:3<324::AID-PROT8>3.0.CO;2-H CrossRefPubMedGoogle Scholar
- Kinjo AR, Bekker G-J, Suzuki H, Tsuchiya Y, Kawabata T, Ikegawa Y, Nakamura H (2017) Protein Data Bank Japan (PDBj): updated user interfaces, resource description framework, analysis tools for large structures. Nucleic Acids Res 45:D282–D288. https://doi.org/10.1093/nar/gkw962 CrossRefPubMedGoogle Scholar
- Malkowski MG, Martin PD, Guzik JC, Edwards BF (1997) The co-crystal structure of unliganded bovine α-thrombin and prethrombin-2: movement of the Tyr-Pro-Pro-Trp segment and active site residues upon ligand binding. Protein Sci 6:1438–1448. https://doi.org/10.1002/pro.5560060708 CrossRefPubMedPubMedCentralGoogle Scholar
- Momany FA, McGuire RF, Burgess AW, Scheraga HA (1975) Energy parameters in polypeptides. VII. Geometric parameters, partial atomic charges, nonbonded interactions, hydrogen bond interactions, and intrinsic torsional potentials for the naturally occurring amino acids. J Phys Chem 79:2361–2381. https://doi.org/10.1021/j100589a006 CrossRefGoogle Scholar
- Najmanovich R, Kuttner J, Sobolev V, Edelman M (2000) Side-chain flexibility in proteins upon ligand binding. Proteins 39:261–268. https://doi.org/10.1002/(SICI)1097-0134(20000515)39:3<261::AID-PROT90>3.0.CO;2-4 CrossRefPubMedGoogle Scholar
- Raimondi F, Felline A, Seeber M, Mariani S, Fanelli F (2013) A mixed protein structure network and elastic network model approach to predict the structural communication in biomolecular systems: the PDZ2 domain from tyrosine phosphatase 1E as a case study. J Chem Theory Comput 9:2504–2518. https://doi.org/10.1021/ct400096f CrossRefPubMedGoogle Scholar
- Rodgers TL, Townsend PD, Burnell D, Jones ML, Richards SA, McLeish TC, Pohl E, Wilson MR, Cann MJ (2013) Modulation of global low-frequency motions underlies allosteric regulation: demonstration in CRP/FNR family transcription factors. PLoS Biol 11:e1001651. https://doi.org/10.1371/journal.pbio.1001651 CrossRefPubMedPubMedCentralGoogle Scholar
- Wako H, Endo S (2013) Normal mode analysis based on an elastic network model for biomolecules in the Protein Data Bank, which uses dihedral angles as independent variables. Comput Biol Chem 44:22–30. https://doi.org/10.1016/j.compbiolchem.2013.02.006 CrossRefPubMedGoogle Scholar
- Wako H, Tachikawa M, Ogawa A (1996) A comparative study of dynamic structures between phage 434 Cro and repressor proteins by normal mode analysis. Proteins 26:72–80. https://doi.org/10.1002/(SICI)1097-0134(199609)26:1<72::AID-PROT7>3.0.CO;2-I CrossRefPubMedGoogle Scholar