PMID- 26579774
OWN - NLM
STAT- MEDLINE
DCOM- 20160627
LR  - 20151120
IS  - 1549-9626 (Electronic)
IS  - 1549-9618 (Linking)
VI  - 11
IP  - 3
DP  - 2015 Mar 10
TI  - Bottom-Up Coarse-Graining of Peptide Ensembles and Helix-Coil Transitions.
PG  - 1278-91
LID - 10.1021/ct5009922 [doi]
AB  - This work investigates the capability of bottom-up methods for parametrizing 
      minimal coarse-grained (CG) models of disordered and helical peptides. We 
      consider four high-resolution peptide ensembles that demonstrate varying degrees 
      of complexity. For each high-resolution ensemble, we parametrize a CG model via 
      the multiscale coarse-graining (MS-CG) method, which employs a generalized 
      Yvon-Born-Green (g-YBG) relation to determine potentials directly (i.e., without 
      iteration) from the high-resolution ensemble. The MS-CG method accurately 
      describes high-resolution models that fluctuate about a single conformation. 
      However, given the minimal resolution and simple molecular mechanics potential, 
      the MS-CG method provides a less accurate description for a high-resolution 
      peptide model that samples a disordered ensemble with multiple distinct 
      conformations. We employ an iterative g-YBG method to develop a CG model that 
      more accurately describes the relevant distribution functions and free energy 
      surfaces for this disordered ensemble. Nevertheless, this more accurate model 
      does not reproduce the cooperative helix-coil transition that is sampled by the 
      high resolution model. By comparing the different models, we demonstrate that the 
      errors in the MS-CG model primarily stem from the lack of cooperative 
      interactions afforded by the minimal representation and molecular mechanics 
      potential. This work demonstrates the potential of the MS-CG method for 
      accurately modeling complex biomolecular structures, but also highlights the 
      importance of more complex potentials for modeling cooperative transitions with a 
      minimal CG representation.
FAU - Rudzinski, Joseph F
AU  - Rudzinski JF
AD  - Department of Chemistry, The Pennsylvania State University , University Park, 
      Pennsylvania 16802, United States.
FAU - Noid, William G
AU  - Noid WG
AD  - Department of Chemistry, The Pennsylvania State University , University Park, 
      Pennsylvania 16802, United States.
LA  - eng
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.
DEP - 20150225
PL  - United States
TA  - J Chem Theory Comput
JT  - Journal of chemical theory and computation
JID - 101232704
RN  - 0 (Peptides)
SB  - IM
MH  - *Molecular Dynamics Simulation
MH  - Peptides/*chemistry
EDAT- 2015/11/19 06:00
MHDA- 2016/06/28 06:00
CRDT- 2015/11/19 06:00
PHST- 2015/11/19 06:00 [entrez]
PHST- 2015/11/19 06:00 [pubmed]
PHST- 2016/06/28 06:00 [medline]
AID - 10.1021/ct5009922 [doi]
PST - ppublish
SO  - J Chem Theory Comput. 2015 Mar 10;11(3):1278-91. doi: 10.1021/ct5009922. Epub 
      2015 Feb 25.