15N-H-Related Conformational Entropy Changes Entailed by Plexin-B1 RBD Dimerization: Combined Molecular Dynamics/NMR Relaxation Approach

Mirco Zerbetto, Eva Meirovitch

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


We report on a new method for determining function-related conformational entropy changes in proteins. Plexin-B1 RBD dimerization serves as example, and internally mobile N-H bonds serve as probes. Sk (entropy in units of kBT) is given by -∫(PeqlnPeq)dΩ, where Peq = exp(-u) is the probability density for probe orientation, and u the local potential. Previous slowly relaxing local structure (SRLS) analyses of 15N-H relaxation in proteins determined linear combinations of D002(Ω) and (D022(Ω) + D0-22(Ω)) (D0KL(Ω) represents a Wigner rotation matrix element in uniaxial local medium) as "best-fit" form of u. SRLS also determined the "best-fit" orientation of the related ordering tensor. On the basis of this information the coefficients (in the linear combination) of the terms specified above are determined with molecular dynamics (MD) simulations. With the explicit expression for u thus in hand, Sk is calculated. We find that in general Sk decreases, i.e., the local order increases, upon plexin-B1 RBD dimerization. The largest decrease in Sk occurs in the helices α1 and α2, followed by the α26 turn. Only the relatively small peripheral β2 strand, β21 turn, and L3 loop become more disordered. That α-helices dominate ΔSk = Sk(dimer) - Sk(monomer), a few peripheral outliers partly counterbalance the overall decrease in Sk, and the probability density function, Peq, has rhombic symmetry given that the underlying potential function, u, has rhombic symmetry, are interesting features. We also derive S2 (the proxy of u in the simple "model-free (MF)" limit of SRLS) with MD. Its conversion into a potential requires assumptions and adopting a simple axial form of u. Ensuing ΔSk(MF) profiles are u-dependent and differ from ΔSk(SRLS). A method that provides consistent, general, and accurate Sk, atomistic/mesoscopic in nature, has been developed. Its ability to provide new insights in protein research has been illustrated.

Original languageEnglish
Pages (from-to)3007-3015
Number of pages9
JournalJournal of Physical Chemistry B
Issue number14
StatePublished - 13 Apr 2017

Bibliographical note

Funding Information:
This work was supported by the Israel Science Foundation (Grant No. 369/15 to E.M.). Part of this work was carried out by Dr. Mirco Zerbetto at Case Western Reserve University, Cleveland, OH, in the group of Prof. Matthias Buck; his hospitality is gratefully acknowledged. We acknowledge fruitful discussions with Prof. Buck, and Prof. Antonino Polimeno of the University of Padova.

Publisher Copyright:
© 2017 American Chemical Society.


Dive into the research topics of '15N-H-Related Conformational Entropy Changes Entailed by Plexin-B1 RBD Dimerization: Combined Molecular Dynamics/NMR Relaxation Approach'. Together they form a unique fingerprint.

Cite this