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Replica exchange molecular dynamics simulation of structure variation from α/4β-fold to 3α-fold protein

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Abstract

Replica exchange molecular dynamics (REMD) simulation provides an efficient conformational sampling tool for the study of protein folding. In this study, we explore the mechanism directing the structure variation from α/4β-fold protein to 3α-fold protein after mutation by conducting REMD simulation on 42 replicas with temperatures ranging from 270 K to 710 K. The simulation began from a protein possessing the primary structure of GA88 but the tertiary structure of GB88, two G proteins with “high sequence identity.” Albeit the large Cα-root mean square deviation (RMSD) of the folded protein (4.34 Å at 270 K and 4.75 Å at 304 K), a variation in tertiary structure was observed. Together with the analysis of secondary structure assignment, cluster analysis and principal component, it provides insights to the folding and unfolding pathway of 3α-fold protein and α/4β-fold protein respectively paving the way toward the understanding of the ongoings during conformational variation.

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Acknowledgments

DWZ is supported in part by Nanyang Technological University (NTU) start-up grant, and in part by Singapore Academic Research Fund (AcRF) Tier 1 Grant of M52110095. DWZ would like to acknowledge and thank NTU High Performance Computing (HPC) support and resources. YM is supported by National Natural Science Foundation of China (Grants No. 20803034).

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Authors and Affiliations

  1. Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore, 637371, Singapore

    Raudah Lazim & Dawei Zhang

  2. State Key Laboratory of Precision Spectroscopy, East China Normal University, Shanghai, 200062, China

    Ye Mei

Authors
  1. Raudah Lazim
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  2. Ye Mei
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  3. Dawei Zhang
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Correspondence to Dawei Zhang.

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Fig. S1

Cα-RMSD of H1 (residue 9 to 23), H2 (residue 27 to 34) and H3 (residue 39 to 51) domain of the 3α-GA88 with reference to the NMR structure of GA88 (PDB code: 2JWS)4 at 304 K. (DOC 267 kb)

Fig. S2

Conformational evolution of the unfolding of α/4β-GA88 based on the temporal activity of the protein projected from five eigenvectors, i.e., PC at 270 K and 304 K for the first 15 ns. (DOC 652 kb)

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Lazim, R., Mei, Y. & Zhang, D. Replica exchange molecular dynamics simulation of structure variation from α/4β-fold to 3α-fold protein. J Mol Model 18, 1087–1095 (2012). https://doi.org/10.1007/s00894-011-1147-8

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  • DOI: https://doi.org/10.1007/s00894-011-1147-8

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