Local Ordering at Mobile Sites in Proteins: Combining Perspectives from NMR Relaxation and Molecular Dynamics

Oren Tchaicheeyan, Netanel Mendelman, Mirco Zerbetto, Eva Meirovitch

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


We report on progress toward improving NMR relaxation analysis in proteins in terms of the slowly relaxing local structure (SRLS) approach by developing a method that combines SRLS with molecular dynamics (MD) simulations. 15 N-H bonds from the Rho GTPase binding domain of plexin-B1 are used as test case. We focus on the locally restricting/ordering potential of mean force (POMF), u(), at the N-H site (and specify the orientation of the N-H bond in the protein). In SRLS, u() is expanded in the basis set of the real linear combinations of the Wigner rotation matrix elements with M = 0, D L,|K| (). Because of limited data sensitivity, only the lowest (L = 2) terms are preserved; this potential function is denoted by u(SRLS). In MD, the force-field-parametrized POMF is the potential, u (MD) , defined in terms of the probability distribution, Peq(MD) exp( (MD) ). Peq(MD), and subsequently u (MD) , can be derived from the MD trajectory as histograms. One might contemplate utilizing u (MD) instead of u (SRLS) however, histograms cannot be used in SRLS analyses. Here, we approximate u(in terms of linear combinations of the D L,|K| functions with L = 1-4 and appropriate symmetry, denoted by u (DLK) , and optimize the latter (via P eq ) against u (MD) . This yields for every N-H bond an analytical ordering potential, u (DLK-BEST) , which exceeds u (SRLS) considerably in accuracy. u (DLK-BEST) can be used fixed in SRLS data fitting, thereby enabling the determination of additional parameters. This yields a substantially improved picture of structural dynamics, which is a significant benefit. The primary achievement of this work is to have employed for the first time MD data to derive a suitable (in terms of composition and symmetry) approximation to the SRLS POMF.

Original languageEnglish
Pages (from-to)2745-2755
Number of pages11
JournalJournal of Physical Chemistry B
Issue number13
StatePublished - 4 Apr 2019

Bibliographical note

Funding Information:
The authors acknowledge support from the Israel Science Foundation (grant 369/15 to E.M.) and the Binational Israel-U.S.A. Science Foundation (grant 2016097 to E.M. and J. H. Freed).

Publisher Copyright:
Copyright © 2019 American Chemical Society.


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