PMID- 20550147
OWN - NLM
STAT- MEDLINE
DCOM- 20100927
LR  - 20100701
IS  - 1520-5207 (Electronic)
IS  - 1520-5207 (Linking)
VI  - 114
IP  - 26
DP  - 2010 Jul 8
TI  - Molecular dynamics simulations of polyglutamine aggregation using solvent-free 
      multiscale coarse-grained models.
PG  - 8735-43
LID - 10.1021/jp1007768 [doi]
AB  - The multiscale coarse-graining (MS-CG) method is used to construct solvent-free 
      CG models for polyglutamine peptides having various repeat lengths. Because the 
      resulting CG models have fewer degrees of freedom than a corresponding all-atom 
      simulations, they make it possible to study the self-assembly of polyglutamines 
      at high concentrations for the first time by allowing for better equilibration 
      and statistical sampling that is well beyond the range achievable by all-atom 
      models. Molecular dynamics (MD) simulations performed with these models show that 
      polyglutamine monomers with repeat lengths < or = 28 fluctuate between their 
      folded and unfolded states. Monomers with 32 or more residues are stable and form 
      alpha-helix solid structures. The degree of monomer compactness increases with 
      chain length in both cases. CG MD simulations of equilibrium polyglutamine 
      aggregates show that even at high concentrations, the system statistically 
      fluctuates between heterogeneous and homogeneous configurations, rather than 
      simply aggregates. The degree of aggregation and fluctuation increases with 
      concentration and chain length. All of these phenomena are consistent with the 
      experimental observations and may be explained by a mechanism that the collective 
      nonbonded interactions between polyglutamine molecules in water solution are only 
      weakly attractive. Finally, this work demonstrates that computer simulation of 
      polypeptides self-assembly and aggregation, which is presently beyond the reach 
      of all-atom MD simulations, is attainable using solvent-free MS-CG models.
FAU - Wang, Yanting
AU  - Wang Y
AD  - Key Laboratory of Frontiers in Theoretical Physics, Institute of Theoretical 
      Physics, Chinese Academy of Sciences, 55 East Zhongguancun Road, Beijing, 100190 
      China.
FAU - Voth, Gregory A
AU  - Voth GA
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - J Phys Chem B
JT  - The journal of physical chemistry. B
JID - 101157530
RN  - 0 (Peptides)
RN  - 0 (Solvents)
RN  - 26700-71-0 (polyglutamine)
SB  - IM
MH  - Dimerization
MH  - *Molecular Dynamics Simulation
MH  - Peptides/*chemistry
MH  - Protein Conformation
MH  - Solvents/chemistry
EDAT- 2010/06/17 06:00
MHDA- 2010/09/29 06:00
CRDT- 2010/06/17 06:00
PHST- 2010/06/17 06:00 [entrez]
PHST- 2010/06/17 06:00 [pubmed]
PHST- 2010/09/29 06:00 [medline]
AID - 10.1021/jp1007768 [doi]
PST - ppublish
SO  - J Phys Chem B. 2010 Jul 8;114(26):8735-43. doi: 10.1021/jp1007768.