PMID- 16203982
OWN - NLM
STAT- MEDLINE
DCOM- 20060420
LR  - 20240510
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 102
IP  - 41
DP  - 2005 Oct 11
TI  - Characterization of the folding landscape of monomeric lactose repressor: 
      quantitative comparison of theory and experiment.
PG  - 14569-74
AB  - Recent theoretical/computational studies based on simplified protein models and 
      experimental investigation have suggested that the native structure of a protein 
      plays a primary role in determining the folding rate and mechanism of relatively 
      small single-domain proteins. Here, we extend the study of the relationship 
      between protein topology and folding mechanism to a larger protein with complex 
      topology, by analyzing the folding process of monomeric lactose repressor (MLAc) 
      computationally by using a Go-like C(alpha) model. Next, we combine simulation 
      and experimental results (see companion article in this issue) to achieve a 
      comprehensive assessment of the folding landscape of this protein. Remarkably, 
      simulated kinetic and equilibrium analyses show an excellent quantitative 
      agreement with the experimental folding data of this study. The results of this 
      comparison show that a simplified, completely unfrustrated C(alpha) model 
      correctly reproduces the complex folding features of a large multidomain protein 
      with complex topology. The success of this effort underlines the importance of 
      synergistic experimental/theoretical approaches to achieve a broader 
      understanding of the folding landscape.
FAU - Das, Payel
AU  - Das P
AD  - Department of Chemistry, Rice University, Houston, TX 77005, USA.
FAU - Wilson, Corey J
AU  - Wilson CJ
FAU - Fossati, Giovanni
AU  - Fossati G
FAU - Wittung-Stafshede, Pernilla
AU  - Wittung-Stafshede P
FAU - Matthews, Kathleen S
AU  - Matthews KS
FAU - Clementi, Cecilia
AU  - Clementi C
LA  - eng
GR  - R01 GM059663/GM/NIGMS NIH HHS/United States
GR  - GM08280/GM/NIGMS NIH HHS/United States
GR  - T32 GM008280/GM/NIGMS NIH HHS/United States
GR  - GM059663/GM/NIGMS NIH HHS/United States
GR  - R01 GM022441/GM/NIGMS NIH HHS/United States
GR  - GM22441/GM/NIGMS NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20051003
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Bacterial Proteins)
RN  - 0 (Lac Repressors)
RN  - 0 (Repressor Proteins)
SB  - IM
MH  - Bacterial Proteins/*chemistry
MH  - Biophysical Phenomena
MH  - Biophysics
MH  - Computer Simulation
MH  - Kinetics
MH  - Lac Repressors
MH  - *Models, Molecular
MH  - *Protein Folding
MH  - Repressor Proteins/*chemistry
PMC - PMC1253569
EDAT- 2005/10/06 09:00
MHDA- 2006/04/21 09:00
PMCR- 2006/04/11
CRDT- 2005/10/06 09:00
PHST- 2005/10/06 09:00 [pubmed]
PHST- 2006/04/21 09:00 [medline]
PHST- 2005/10/06 09:00 [entrez]
PHST- 2006/04/11 00:00 [pmc-release]
AID - 0505844102 [pii]
AID - 010214569 [pii]
AID - 10.1073/pnas.0505844102 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2005 Oct 11;102(41):14569-74. doi: 
      10.1073/pnas.0505844102. Epub 2005 Oct 3.