PMID- 30702887
OWN - NLM
STAT- MEDLINE
DCOM- 20190326
LR  - 20200309
IS  - 1549-9626 (Electronic)
IS  - 1549-9618 (Print)
IS  - 1549-9618 (Linking)
VI  - 15
IP  - 3
DP  - 2019 Mar 12
TI  - Systematic Coarse-Grained Lipid Force Fields with Semiexplicit Solvation via 
      Virtual Sites.
PG  - 2087-2100
LID - 10.1021/acs.jctc.8b01033 [doi]
AB  - Despite the central role of lipids in many biophysical functions, the molecular 
      mechanisms that dictate macroscopic lipid behavior remain elusive to both 
      experimental and computational approaches. As such, there has been much interest 
      in the development of low-resolution, implicit-solvent coarse-grained (CG) models 
      to dynamically simulate biologically relevant spatiotemporal scales with 
      molecular fidelity. However, in the absence of solvent, a key challenge for CG 
      models is to faithfully emulate solvent-mediated forces, which include both 
      hydrophilic and hydrophobic interactions that drive lipid aggregation and 
      self-assembly. In this work, we provide a new methodological framework to 
      incorporate semiexplicit solvent effects through the use of virtual CG particles, 
      which represent structural features of the solvent-lipid interface. To do so, we 
      leverage two systematic coarse-graining approaches, multiscale coarse-graining 
      (MS-CG) and relative entropy minimization (REM), in a hybrid fashion to construct 
      our virtual-site CG (VCG) models. As a proof-of-concept, we focus our efforts on 
      two lipid species, 1,2-dioleoyl- sn-glycero-3-phosphocholine (DOPC) and 
      1,2-dipalmitoyl- sn-glycero-3-phosphocholine (DPPC), which adopt a 
      liquid-disordered and gel phase, respectively, at room temperature. Through our 
      analysis, we also present, to our knowledge, the first direct comparison between 
      the MS-CG and REM methods for a complex biomolecule and highlight each of their 
      strengths and weaknesses. We further demonstrate that VCG models recapitulate the 
      rich biophysics of lipids, which enable self-assembly, morphological diversity, 
      and multiple phases. Our findings suggest that the VCG framework is a powerful 
      approach for investigation into macromolecular biophysics.
FAU - Pak, Alexander J
AU  - Pak AJ
AD  - Department of Chemistry , The University of Chicago , Chicago , Illinois 60637 , 
      United States.
FAU - Dannenhoffer-Lafage, Thomas
AU  - Dannenhoffer-Lafage T
AD  - Department of Chemistry , The University of Chicago , Chicago , Illinois 60637 , 
      United States.
FAU - Madsen, Jesper J
AU  - Madsen JJ
AD  - Department of Chemistry , The University of Chicago , Chicago , Illinois 60637 , 
      United States.
FAU - Voth, Gregory A
AU  - Voth GA
AUID- ORCID: 0000-0002-3267-6748
AD  - Department of Chemistry , The University of Chicago , Chicago , Illinois 60637 , 
      United States.
LA  - eng
GR  - F32 GM125218/GM/NIGMS NIH HHS/United States
GR  - R01 GM063796/GM/NIGMS NIH HHS/United States
PT  - Journal Article
DEP - 20190215
PL  - United States
TA  - J Chem Theory Comput
JT  - Journal of chemical theory and computation
JID - 101232704
RN  - 0 (Lipid Bilayers)
RN  - 0 (Phosphatidylcholines)
RN  - 0 (Solvents)
RN  - 2644-64-6 (1,2-Dipalmitoylphosphatidylcholine)
RN  - 319X2NFW0A (colfosceril palmitate)
RN  - EDS2L3ODLV (1,2-oleoylphosphatidylcholine)
SB  - IM
MH  - 1,2-Dipalmitoylphosphatidylcholine/*analogs & derivatives/chemistry
MH  - *Entropy
MH  - Lipid Bilayers/*chemistry
MH  - Molecular Dynamics Simulation
MH  - Phase Transition
MH  - Phosphatidylcholines/*chemistry
MH  - Solvents/chemistry
MH  - Temperature
PMC - PMC6416712
COIS- The authors declare no competing financial interest.
EDAT- 2019/02/01 06:00
MHDA- 2019/03/27 06:00
PMCR- 2019/03/14
CRDT- 2019/02/01 06:00
PHST- 2019/02/01 06:00 [pubmed]
PHST- 2019/03/27 06:00 [medline]
PHST- 2019/02/01 06:00 [entrez]
PHST- 2019/03/14 00:00 [pmc-release]
AID - 10.1021/acs.jctc.8b01033 [doi]
PST - ppublish
SO  - J Chem Theory Comput. 2019 Mar 12;15(3):2087-2100. doi: 10.1021/acs.jctc.8b01033. 
      Epub 2019 Feb 15.