[NMR paper] Conformational Entropy from NMR Relaxation in Proteins: the SRLS Perspective.

[nmrlearner]

Conformational Entropy from NMR Relaxation in Proteins: the SRLS Perspective.

Related Articles Conformational Entropy from NMR Relaxation in Proteins: the SRLS Perspective.

J Phys Chem B. 2017 Jan 06;:

Authors: Tchaicheeyan O, Meirovitch E

Abstract
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-CDH2 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 potential, u(?)?. The latter yields the orientational probability density, Peq = exp(-?u(?)?), hence the related conformational entropy, Š=-?Peq(?) ln[Peq(?)]sin? d? (Š is "entropy" in units of kBT, and ? 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?1 (PLC?1C SH2), the construct dihydrofolate reductase-E:folate (DHFR-E:folate), and their complexes with appropriate ligands, to determine ?Š. 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. In all of these cases simple SRLS models are suitable. Upon ligand-binding the backbones of 4-OT, ACBP and PLC?1C SH2 show limited, increased and decreased order, respectively; the cores of DHFR-E:folate and PLC?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 important in determining ?Š. The consistent and general tool developed herein is expected to provide further insight in future work.


PMID: 28059521 [PubMed - as supplied by publisher]



More...