PMID- 23786631
OWN - NLM
STAT- MEDLINE
DCOM- 20140522
LR  - 20131024
IS  - 1520-5207 (Electronic)
IS  - 1520-5207 (Linking)
VI  - 117
IP  - 42
DP  - 2013 Oct 24
TI  - Double resolution model for studying TMAO/water effective interactions.
PG  - 13268-77
LID - 10.1021/jp403635g [doi]
AB  - The structural properties of water molecules surrounding TMAO molecules are 
      studied using a newly developed atomistic force field for TMAO, combined with a 
      multiscale coarse-graining (MS-CG) force field derived from the atomistic 
      simulations. The all-atom force field is parametrized to work with the OPLS force 
      field and with SPC, TIP3P, and TIP4P water models. The dual-resolution modeling 
      enables a complete study of the dynamical and structural properties of the 
      system, with the CG model providing important new physical insights into which 
      interactions are critical in determining the structure of water around TMAO. TMAO 
      is an osmolyte that stabilizes protein structures under conditions of chemical, 
      thermal, and pressure denaturation. This molecule is excluded from the surface of 
      proteins, and its effect on protein stability is mediated through TMAO-water 
      interactions. We find that TMAO strongly binds two to three water molecules and, 
      surprisingly, that methyl groups repel both the other methyl groups of TMAO and 
      water molecules alike. The latter result is important because it shows that 
      methyl groups are not interacting with each other through the expected 
      hydrophobic effect (which would be attractive and not repulsive) and that the 
      repulsion of water molecules forces a clathrate-like hydrogen bond network around 
      them. We speculate that TMAO is excluded from the vicinity of the protein because 
      the peculiar structure of water around TMAO prevents this molecule from coming in 
      close contact with the protein.
FAU - Larini, Luca
AU  - Larini L
AD  - Department of Chemistry and Biochemistry and of Physics, University of 
      California, Santa Barbara , Santa Barbara, California 93106, United States.
FAU - Shea, Joan-Emma
AU  - Shea JE
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20130708
PL  - United States
TA  - J Phys Chem B
JT  - The journal of physical chemistry. B
JID - 101157530
RN  - 0 (Methylamines)
RN  - 0 (Proteins)
RN  - 059QF0KO0R (Water)
RN  - FLD0K1SJ1A (trimethyloxamine)
SB  - IM
MH  - Hydrogen Bonding
MH  - Hydrophobic and Hydrophilic Interactions
MH  - Methylamines/*chemistry
MH  - Molecular Dynamics Simulation
MH  - Pressure
MH  - Protein Denaturation
MH  - Proteins/chemistry/metabolism
MH  - Water/*chemistry
EDAT- 2013/06/22 06:00
MHDA- 2014/05/23 06:00
CRDT- 2013/06/22 06:00
PHST- 2013/06/22 06:00 [entrez]
PHST- 2013/06/22 06:00 [pubmed]
PHST- 2014/05/23 06:00 [medline]
AID - 10.1021/jp403635g [doi]
PST - ppublish
SO  - J Phys Chem B. 2013 Oct 24;117(42):13268-77. doi: 10.1021/jp403635g. Epub 2013 
      Jul 8.