PMID- 28101951
OWN - NLM
STAT- MEDLINE
DCOM- 20191127
LR  - 20191127
IS  - 1096-987X (Electronic)
IS  - 0192-8651 (Linking)
VI  - 38
IP  - 16
DP  - 2017 Jun 15
TI  - Rigidity and flexibility in the tetrasaccharide linker of proteoglycans from 
      atomic-resolution molecular simulation.
PG  - 1438-1446
LID - 10.1002/jcc.24738 [doi]
AB  - Proteoglycans (PGs) are covalent conjugates between protein and carbohydrate 
      (glycosaminoglycans). Certain classes of glycosaminoglycans such as chondroitin 
      sulfate/dermatan sulfate and heparan sulfate utilize a specific tetrasaccharide 
      linker for attachment to the protein component: 
      GlcAbeta1-3Galbeta1-3Galbeta1-4Xylbeta1-O-Ser. Toward understanding the conformational 
      preferences of this linker, the present work used all-atom explicit-solvent 
      molecular dynamics (MD) simulations combined with Adaptive Biasing Force (ABF) 
      sampling to determine high-resolution, high-precision conformational free energy 
      maps DeltaG(phi, psi) for each glycosidic linkage between constituent disaccharides, 
      including the variant where GlcA is substituted with IdoA. These linkages are 
      characterized by single, predominant (> 97% occupancy), and broad (45 degrees  x 60 degrees  for 
      DeltaG(phi, psi) < 1 kcal/mol) free-energy minima, while the Xyl-Ser linkage has two such 
      minima similar in free-energy, and additional flexibility from the Ser sidechain 
      dihedral. Conformational analysis of microsecond-scale standard MD on the 
      complete tetrasaccharide-O-Ser conjugate is consistent with ABF data, suggesting 
      (phi, psi) probabilities are independent of the linker context, and that the 
      tetrasaccharide acts as a relatively rigid unit whereas significant 
      conformational heterogeneity exists with respect to rotation about bonds 
      connecting Xyl to Ser. (c) 2017 Wiley Periodicals, Inc.
CI  - (c) 2017 Wiley Periodicals, Inc.
FAU - Ng, Cathy
AU  - Ng C
AD  - Department of Pharmaceutical Sciences, University of New England College of 
      Pharmacy, 716 Stevens Avenue, Portland, Maine, 04103.
FAU - Nandha Premnath, Padmavathy
AU  - Nandha Premnath P
AD  - Department of Pharmaceutical Sciences, University of New England College of 
      Pharmacy, 716 Stevens Avenue, Portland, Maine, 04103.
FAU - Guvench, Olgun
AU  - Guvench O
AUID- ORCID: 0000-0001-5673-7026
AD  - Department of Pharmaceutical Sciences, University of New England College of 
      Pharmacy, 716 Stevens Avenue, Portland, Maine, 04103.
AD  - Graduate School of Biomedical Science and Engineering, University of Maine, 5775 
      Stodder Hall, Orono, Maine, 04469.
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20170119
PL  - United States
TA  - J Comput Chem
JT  - Journal of computational chemistry
JID - 9878362
RN  - 0 (Disaccharides)
RN  - 0 (Glycosaminoglycans)
RN  - 0 (Oligosaccharides)
RN  - 0 (Proteoglycans)
RN  - 0 (dermatan sulfate chondroitin sulfate)
RN  - 24967-94-0 (Dermatan Sulfate)
RN  - 9007-28-7 (Chondroitin Sulfates)
SB  - IM
MH  - Biomechanical Phenomena
MH  - Biophysical Phenomena
MH  - Chondroitin Sulfates/chemistry
MH  - Dermatan Sulfate/analogs & derivatives/chemistry
MH  - Disaccharides/chemistry
MH  - Glycosaminoglycans/chemistry
MH  - Molecular Dynamics Simulation
MH  - Oligosaccharides/*chemistry
MH  - Protein Conformation
MH  - Proteoglycans/*chemistry
OTO - NOTNLM
OT  - conformation
OT  - glycosaminoglycan
OT  - glycosidic linkage
OT  - linker
OT  - molecular dynamics
OT  - proteoglycan
OT  - tetrasaccharide
EDAT- 2017/01/20 06:00
MHDA- 2019/11/28 06:00
CRDT- 2017/01/20 06:00
PHST- 2016/09/08 00:00 [received]
PHST- 2016/12/12 00:00 [revised]
PHST- 2016/12/20 00:00 [accepted]
PHST- 2017/01/20 06:00 [pubmed]
PHST- 2019/11/28 06:00 [medline]
PHST- 2017/01/20 06:00 [entrez]
AID - 10.1002/jcc.24738 [doi]
PST - ppublish
SO  - J Comput Chem. 2017 Jun 15;38(16):1438-1446. doi: 10.1002/jcc.24738. Epub 2017 
      Jan 19.