PMID- 28059521
OWN - NLM
STAT- MEDLINE
DCOM- 20180501
LR  - 20180501
IS  - 1520-5207 (Electronic)
IS  - 1520-5207 (Linking)
VI  - 121
IP  - 4
DP  - 2017 Feb 2
TI  - Conformational Entropy from NMR Relaxation in Proteins: The SRLS Perspective.
PG  - 758-768
LID - 10.1021/acs.jpcb.6b13034 [doi]
AB  - Conformational entropy changes associated with bond-vector motions in proteins 
      contribute to the free energy of ligand-binding. To derive such contributions, we 
      apply the slowly relaxing local structure (SRLS) approach to NMR relaxation from 
      (15)N-H bonds or C-CDH(2) moieties of several proteins in free and ligand-bound 
      form. The spatial restraints on probe motion, which determine the extent of local 
      order, are expressed in SRLS by a well-defined potential, u(theta). The latter yields 
      the orientational probability density, P(eq) = exp(-u(theta)), and hence the related 
      conformational entropy, S = -integralP(eq)(theta) ln[P(eq)(theta)] sin theta dtheta (S is "entropy" in 
      units of k(B)T, and theta represents the bond-vector orientation in the protein). 
      SRLS is applied to 4-oxalocrotonate tautomerase (4-OT), the acyl-coenzyme A 
      binding protein (ACBP), the C-terminal SH2 domain of phospholipase C(gamma)1 
      (PLC(gamma)1C SH2), the construct dihydrofolate reductase-E:folate (DHFR-E:folate), 
      and their complexes with appropriate ligands, to determine DeltaS. Eglin C and its 
      V18A and V34A mutants are also studied. Finally, SRLS is applied to the 
      structurally homologous proteins TNfn3 and FNfn10 to characterize within its 
      scope the unusual "dynamics" of the TNfn3 core. Upon ligand-binding, the 
      backbones of 4-OT, ACBP, and PLC(gamma)1C SH2 show limited, increased, and decreased 
      order, respectively; the cores of DHFR-E:folate and PLC(gamma)1C SH2 become more 
      ordered. The V18A (V34A) mutation increases (decreases) the order within the 
      eglin C core. The core of TNfn3 is less ordered structurally and more mobile 
      kinetically. Secondary structure versus loops, surface-binding versus core 
      insertion, and ligand size emerged as being important in rationalizing DeltaS. The 
      consistent and general tool developed herein is expected to provide further 
      insights in future work.
FAU - Tchaicheeyan, Oren
AU  - Tchaicheeyan O
AD  - The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University , 
      Ramat-Gan 52900 Israel.
FAU - Meirovitch, Eva
AU  - Meirovitch E
AUID- ORCID: 0000-0001-5117-5079
AD  - The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University , 
      Ramat-Gan 52900 Israel.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170124
PL  - United States
TA  - J Phys Chem B
JT  - The journal of physical chemistry. B
JID - 101157530
RN  - 0 (Proteins)
SB  - IM
MH  - *Entropy
MH  - Molecular Dynamics Simulation
MH  - *Nuclear Magnetic Resonance, Biomolecular
MH  - Protein Conformation
MH  - Proteins/*chemistry
EDAT- 2017/01/07 06:00
MHDA- 2018/05/02 06:00
CRDT- 2017/01/07 06:00
PHST- 2017/01/07 06:00 [pubmed]
PHST- 2018/05/02 06:00 [medline]
PHST- 2017/01/07 06:00 [entrez]
AID - 10.1021/acs.jpcb.6b13034 [doi]
PST - ppublish
SO  - J Phys Chem B. 2017 Feb 2;121(4):758-768. doi: 10.1021/acs.jpcb.6b13034. Epub 
      2017 Jan 24.