title: 15N-H-Related Conformational Entropy Changes Entailed By Plexin-B1 RBD Dimerization: Combined Molecular Dynamics/NMR Relaxation Approach.
abstract: 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 of15N-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, Skis calculated. We find that in general Skdecreases, i.e., the local order increases, upon plexin-B1 RBD dimerization. The largest decrease in Skoccurs in the helices α1and α2, followed by the α2/β6turn. Only the relatively small peripheral β2strand, β2/α1turn, 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.
authors.affiliation: Department of Chemical Sciences, University of Padova , Padova 35131, Italy.
authors.forename: Mirco
authors.initials: M
authors.lastname: Zerbetto
authors.affiliation: The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University , Ramat-Gan 52900, Israel.
authors.forename: Eva
authors.identifier: 0000-0001-5117-5079
authors.initials: E
authors.lastname: Meirovitch
mesh_terms: D019277:Entropy; D006801:Humans; D056004:Molecular Dynamics Simulation; D009419:Nerve Tissue Proteins / Q000737:chemistry*; D009587:Nitrogen Isotopes; D019906:Nuclear Magnetic Resonance, Biomolecular; D011487:Protein Conformation; D055503:Protein Multimerization; D011956:Receptors, Cell Surface / Q000737:chemistry*
chemical_list: D009419:Nerve Tissue Proteins; D009587:Nitrogen Isotopes; C492119:PLXNB1 protein, human; D011956:Receptors, Cell Surface