Biology subjects

Stan, R. C.

Publications and source records attributed to Stan, R. C..

3 recordsLinked to original sources

bioRxiv2023

Self-inhibition of HER2 at fever temperatures may prevent dimerization with HER3

BackgroundHER2 receptor is overexpressed in different aggressive and recurrent tumors, and the modulation of its conformational changes has been achieved using immunotherapy or chemotherapy. ObjectiveTo assess the role of fever temperatures on the dynamics of HER2 in the absence of a binding partner. MethodsMolecular dynamics simulations of apo-HER2 were performed at 37{square}-40{square}, in order to gauge its intramolecular dynamics. ResultsHER2 assumes an inactive and "bent" conformation at 40{square}, while it maintains its extended, active conformation that can dimerize with other HER partners, in the 37{square}-39{square} range. ConclusionThese novel results indicate the role of fever temperatures on modulating conformational changes in an essential tumor target. Cancer treatment can leverage the use of thermal therapy at particular fever points, in order to complement existing radio or chemotherapy options.

cancer biology↗

bioRxiv2022

Fever temperatures modulate intraprotein dynamics and enhance the binding affinity between monoclonal antibodies and the Spike protein from SARS-CoV-2

Fever is a typical symptom of most infectious diseases. While prolonged fever may be clinically undesirable, mild reversible fever (< 39{degrees}C, 312K) can potentiate the immune responses against pathogens. Here, using molecular dynamics, we investigated the effect of febrile temperatures (38{degrees}C to 40{degrees}C, 311K to 313K) on the immune complexes formed by the SARS-CoV-2 spike protein with two neutralizing antibodies. We found that, at mild fever temperatures (311-312K), the binding affinities of the two antibodies improve when compared to the physiological body temperature (37{degrees}C, 310K). Furthermore, only at 312K, antibodies exert distinct mechanical effects on the receptor binding domains of the spike protein that may hinder SARS-CoV-2 infectivity. Enhanced antibody binding affinity may thus be obtained using appropriate temperature conditions.

bioinformatics↗

bioRxiv2018

Hysteresis in the thermal relaxation dynamics of an immune complex as basis for molecular memory

Proteins search their vast conformational space in order to attain the native fold and bind productively to relevant biological partners. In particular, most proteins must be able to alternate between at least one active conformational state and back to an inactive conformer, especially for the macromolecules that perform work and need to optimize energy usage. This property may be invoked by a physical stimulus (temperature, radiation) or by a chemical ligand, and may occur through mapping of the protein external environment onto a subset of protein conformers. We have stimulated with temperature cycles two partners of an immune complex before and after assembly, and revealed that properties of the external stimulus (period, phase) are also found in the characteristics of the immune complex (i.e. periodic variations in the binding affinity). These results are important for delineating the bases of molecular memory ex vivo and could serve in the optimization of protein based sensors.

biophysics↗