An SRLS Study of 2H Methyl-Moiety Relaxation and Related Conformational Entropy in Free and Peptide-Bound PLCγ1C SH2

Oren Tchaicheeyan, Eva Meirovitch

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7 Scopus citations

Abstract

The two-body (protein and probe) coupled-rotator slowly relaxing local structure (SRLS) approach for NMR relaxation in proteins is extended to derive conformational entropy, Ŝ. This version of SRLS is applied to deuterium relaxation from the C-CDH2 bonds of free and peptide-bound PLCγ1C SH2. Local C-CDH2 motion is described by a correlation time for local diffusion, τ2, and a Maier-Saupe potential, u. On average, τ2, which largely fulfills τ2 ≪ τ11 - correlation time for global tumbling), is 270 ± 41 ps and u is 2 ± 0.1 kBT. The PLCγ1C SH2 data were analyzed previously with the model-free (MF) method. SRLS is a generalization of MF, assumed so far to yield the latter for τ2 ≪ τ1 and simple local geometry. Despite these conditions being fulfilled, we find here that τ2 and u differ substantially from their MF counterparts. This is shown to stem from MF (a) disregarding mode-coupling of the first type (see below) and (b) parametrizing the methyl-moiety-related spectral density function (SDF). Our main interest lies in ΔŜ, the conformational entropy difference between the peptide-bound and free PLCγ1C SH2 forms. We find that ΔŜ is rendered inaccurate in MF because factors a and b above impair the accuracy of Saxis, the parameter on which the calculation of ΔŜ is based. Conformational entropy was obtained previously using various simple system-specific models. SRLS is unique in obtaining this important thermodynamic quantity based on a general physically well-defined local potential. It is also unique in its ability to extract the information inherent in 2H relaxation parameters from methyl moieties in protein with accuracy commensurate with data sensitivity.

Original languageEnglish
Pages (from-to)10695-10705
Number of pages11
JournalJournal of Physical Chemistry B
Volume120
Issue number41
DOIs
StatePublished - 20 Oct 2016

Bibliographical note

Publisher Copyright:
© 2016 American Chemical Society.

Funding

This work was supported by the Israel Science Foundation (Grant No. 369/15 to E.M.).

FundersFunder number
Israel Science Foundation369/15

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