β-Casein is a component of casein micelle with amphillic nature and is recognized as a "natively disordered" protein that lacks secondary structures. In this study, the temperature and hydration effects on the dynamics of β-casein are explored by quasielastic neutron scattering (QENS). An upturn in the mean square displacement (MSD) of hydrated β-casein indicates an increase of protein flexibility at a temperature of ~225 K. Another increase in MSD at ~100 K, observed in both dry and hydrated β-casein, is ascribed to the methyl group rotations, which are not sensitive to hydration. QENS analysis in the energy domain reveals that the fraction of hydrogen atoms participating in motion in a sphere of diffusion is highly hydration dependent and increases with temperature. In the time domain analysis, a logarithmic-like decay is observed in the range of picosecond to nanosecond (β-relaxation time) in the dynamics of hydrated β-casein. This dynamical behavior has been observed in hydrated globular and oligomeric proteins. Our temperature-dependent QENS experiments provide evidence that lack of a secondary structure in β-casein results in higher flexibility in its dynamics and easier reversible thermal unfolding compared to other rigid biomolecules.

Nontoxic, biocompatible nanodiamonds (ND) have recently been implemented in rational, systematic design of optimal therapeutic use in nanomedicines. However, hydrophilicity of the ND surface strongly influences structure and dynamics of biomolecules that restrict in situ applications of ND. Therefore, fundamental understanding of the impact of hydrophilic ND surface on biomolecules at the molecular level is essential. For tRNA, we observe an enhancement of dynamical behavior in the presence of ND contrary to generally observed slow motion at strongly interacting interfaces. We took advantage of neutron scattering experiments and computer simulations to demonstrate this atypical faster dynamics of tRNA on ND surface. The strong attractive interactions between ND, tRNA, and water give rise to unlike dynamical behavior and structural changes of tRNA in front of ND compared to without ND. Our new findings may provide new design principles for safer, improved drug delivery platforms.

challenge to structural biology. The folded domain structures for the scaffold protein PSD-95 were long known but such fragmentary knowledge lacks methods to assemble these pieces. We used single-molecule FRET studies with multi-parameter fluorescence detection [1] and filtered fluorescence correlation spectroscopy [2, 3] to describe the native state ensemble of this canonical scaffold protein. Our approach represents a solution to describing the flexibility in any multi-domain protein from nanoseconds to seconds. The five domains in PSD-95 partitioned into two independent supramodules. Intramolecular interactions were limited to neighboring domains, which did not interact without being tethered. Although MAGUK proteins are flexible, there are conformational preferences encoded in the primary sequence. [1.] McCann, J. J., Zheng, L. Rohrbeck, D., Felekyan, S., Kühnemuth, R., Sutton, R. B., Seidel, C. A. M., Bowen, M. E.; The supertertiary structure of the synaptic MAGuK scaffold proteins is conserved. Proc. Natl. Acad. Sci. USA. 109, 15775-15780 (2012). [2.] Felekyan, S., Kalinin, S., Sanabria, H., Valeri, A., Seidel, C. A. M.; Filtered FCS: Species auto and cross correlation functions highlight binding and dynamics in biomolecules.

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