Aromatic amino acids buried inside folded proteins play a critical role in stabilizing both the folded conformation and anchoring incoming substrate molecules. Moreover, their ring flips serve as sensitive probes of protein breathing motions. In this work, we accurately estimate the ring-flip rates of a phenylalanine residue in cytochrome C from MD simulations using enhanced sampling methods and advanced rate theories, such as the reactive flux formalism and Grote–Hynes theory (GHT). We demonstrate that the combined steric hindrance from the residues adjacent to the ring, along with their delayed response in accommodating free rotation, manifests as memory-dependent friction. Increasing solvent viscosity slows the fluctuations of these cavity residues, reinforcing the delayed response and producing a fractional viscosity dependence of the flip rate despite the ring being completely buried.
High hydrostatic pressure provides a unique and sensitive perturbation to protein structure, enabling direct measurement of volume changes associated with folding, misfolding, and assembly. Because pressure perturbs noncovalent forces while preserving covalent integrity, it reveals conformational intermediates that o...
J. L. Silva, G. C. de Andrade, M. A. Marques et al.· ACS Applied Polymer Material...· 0 citations
High-pressure processing (HPP) exerts paradoxical effects on myosin, simultaneously promoting molecular unfolding and supramolecular aggregation, yet the underlying mechanisms remain unresolved at atomic resolution. This study employed all-atom molecular dynamics simulations at gradient pressures (0.1-450 MPa) using co...
Xiaoyun Wang, Jie Tang, H. Ramaswamy et al.· Current Research in Food Sci...· 0 citations
Vibrational spectroscopic probes can provide site-specific information on protein structure and dynamics. In this work, the possibility to relate protein motion with the vibrational response for --SCN, --N$_3$, and --SNO labels covalently linked to all alanine-residues in lysozyme is investigated. Depending on the posi...
Simulations have emerged as a pillar in biophysics to understand behavior at the molecular scale, in particular for proteins such as intrinsically disordered proteins. These often show transient folding with long-lived states that are challenging to efficiently sample using conventional simulations. Here, we show that...
T. Bhandari, Kurt Kremer, Martin Girard· bioRxiv· 0 citations
It is demonstrated that hydrophobic amino acids enhance protein thermal stability through a coupled modulation of solvation structure, solvent dynamics, and hydrogen-bonding interactions, with distinct mechanisms depending on side-chain size and aggregation propensity.
This work investigates how protein folding landscapes are altered inside condensates, using the protein α-helix as a model folded domain and develops a chemically specific, residue-resolution model for quantification of α-helical folding and applies it to characterize diverse helices within condensates of varying physi...
Nathaniel Hess, Jerelle A. Joseph· Journal of the American Chem...· 0 citations
A new machine-learning framework aims to improve the success rate of computational protein design while moving away from results that reproduce sequences found in nature.
