Book of Abstracts: Albany 2011

category image Albany 2011
Conversation 17
June 14-18 2011
©Adenine Press (2010)

Molecular Dynamics Simulations on Structural Heterogeneity States of Protein

Well-defined structure proteins can turn into all kinds of structural heterogeneity states such as intermediate state, transition state or unfolded state under different circumstance. Another type of protein, namely intrinsically disordered protein (IDPs), is lacking independently folded states at physiological condition. These states have highly structural heterogeneity (1) and they play central roles in a range of important biological process. It is a formidable challenge to reveal structural character of the flexible and conformatically highly heterogeneous states. Some effective sampling methods such as replica exchange molecular dynamics (REMD) and restraint molecular dynamics simulation (restraint MD) are used to study the disorder states. Here, we gave two cases to study IDPs and protein intermediate state by REMD and restraint MD.

Case 1: Human α-synuclein protein, a presynaptic protein of 140 amino acid residues, is the major component of Lewy bodies (LBs) deposited in the brains of patients with Parkinson’s disease, and it usually has extensive intrinsically disordered regions (IDRs). The N-terminal 12 residues peptide of the α-synuclein (α-syn12) was choosen. The structural and thermodynamics character of α-syn12 peptide in aqueous solution have been investigated by temperature replica exchange molecular dynamics (T-REMD) simulations. The structural and thermodynamic characters of α-syn12 peptide at different pH and temperatures have also been studied by temperature replica exchange molecular dynamics (T-REMD) simulations (2).

Case 2: The other case is to study the thermal intermediate state of high mobility group (HMG) box 5 of human upstream binding factor using the restraint MD simulations. The thermal intermediate state of high mobility group (HMG) box 5 of human upstream binding factor was detected at 55℃ by experimental technique (3), but could not be defined for the sparse data. We performed ensemble-averaged MD simulations to study the intermediate state ensemble of HMG box-5 at 328K with forty-eight replicas for 2.88 . 421 inter-atomic distances derived from NOE and PRE were used as restraints. The results indicated that the intermediate state ensemble presented the structural characteristic of box-5 protein intermediate state and were consistent with experimental results.

The two cases show that molecular dynamics simulation is a powerful route to study structural and thermodynamics characters of the conformational heterogeneous states of protein.

Acknowledgment: Financial support from the Chinese Natural Science Foundation and Shandong Natural Science Foundation (30970561and 31000324) are acknowledged.


  1. M. Vendruscolo, Current Opinion in Structural Biology 17, 15–20 (2007).
  2. Z. Cao, L. Liu and J. Wang, Journal of Biomolecular Structure and Dynamics 28, 343-353 (2010).
  3. Z. Liu, J. Zhang, X. Wang, Y. Ding, J. Wu, and Y. Shi, Proteins: Structure, Function and Bioinformatics 77, 432–447 (2009).

Jihua Wang
Liling Zhao
Zanxia Cao

Key Lab of Biophysics in Shandong (Dezhou University)
Dezhou, China, 253023