Biology subjects

Gideon, D. A.

Publications and source records attributed to Gideon, D. A..

3 recordsLinked to original sources

bioRxiv2026

Thermodynamic Profiling of Glucose Translocation in POPC embedded GLUT-4 protein models

The facilitative transport of hexose through the GLUcose Transporter type 4 (GLUT4) is essential for cellular metabolism and is regulated by allosteric nucleotide interactions. In this study, we conducted a comparative biophysical analysis of glucose translocation using both the native Cryo-EM structure (7WSN) and the AI-predicted AlphaFold model using Steered Molecular Dynamics (SMD) at physiological (310.15 K) and attenuated (303.15 K) temperatures with two different allosteric modulators, ATP and ADP. While the AlphaFold model managed to capture baseline static topologies, dynamic profiling revealed that it intrinsically over-optimizes for static stability, immediately collapsing into a sterically occluded, hyper-packed artifact. Translocation through this constricted geometry forces severe steric solvent exclusion, abruptly stripping the substrates hydration shell and resulting in immediate and immense thermodynamic friction (>300 kJ/mol). Under ATP-bound physiological strain, this hyper-bonded structural clamp prevents functional relaxation, ultimately inducing a catastrophic kinematic failure. Furthermore, ensemble Dynamic Cross-Correlation Matrix (DCCM) analysis demonstrates that the AI-predicted model suffers from persistent rigid-body locking, forcing the transmembrane domain to behave as a kinetically trapped conformation. In contrast, the functionally hydrated Cryo-EM architecture actively maintains a dual-gating pore and successfully isolates the exact mechanical lever driving transport: a native Proline hinge (PRO379) that seamlessly routes allosteric signals from the nucleotide anchor to the pore gate. Within the AlphaFold model, this critical allosteric wiring is disrupted, forcing mechanical coupling through an unphysiological, hyper-correlated aromatic pathway. These findings yield novel atomistic insights into GLUT4 gating mechanics, while definitively establishing that rigid AI-generated architectures lack the essential internal free volume and conformational plasticity required to sustain accurate thermodynamic profiling of dynamic membrane transporters.

biophysics↗

bioRxiv2026

A parsimonious murburn model for microbial motility connects metabolic water ejection to observable mechanical outcomes

The classical model of bacterial flagellar motility posits a rotary engine driven by proton motive force (pmf), with torque generated by stator-rotor interactions and transmitted through a flexible hook to a helical filament. Despite decades of acceptance, this model faces fundamental challenges in thermodynamics, structural mechanics, evolutionary parsimony, and direct observational evidence. We develop and quantitatively test the murburn model, a new paradigm for bacterial motility in which water, produced as an inevitable byproduct of metabolic redox activity, is ejected via the basal secretory module and channelled along the spiral grooves of the flagellar filament. The ejected flow creates a local shear field that induces a transverse bending wave; the precession of this wave is observed as apparent rotation and generates thrust through anisotropic viscous drag, without any rotary motor, ion gradient, or axial rotation. The principal contribution of this work is a self-contained, first-principles treatment of this mechanism: for a unipolar flagellated cell we derive the governing low-Reynolds-number elastohydrodynamic relations from slender-body theory and show that physiologically realistic rates of metabolic water production reproduce the observed swimming speeds and apparent-rotation frequencies at a small fraction of the cellular energy budget, while direct jet propulsion is quantitatively excluded. Building on this derivation, we provide a force-balance comparison of the competing propulsion mechanisms, obtain a set of falsifiable predictions that distinguish the murburn model from the rotary motor, and report a structural analysis of cryo-EM flagellar-hook architectures that reveals solvent-accessible radial canals consistent with lateral water transport. The same single principle accounts for swimming, tumbling, gliding, spirochete undulation, and archaeal motility, without requiring rotating shafts, ion-gradient coupling, or complex switching mechanisms.

biophysics↗

bioRxiv2020

pH and Receptor Induced Confirmational Changes- Implications Towards S1 Dissociation of SARS-CoV2 Spike Glycoprotein

Viruses, being obligate intracellular parasites, must first attach themselves and gain entry into host cells. Viral fusion machinery is the central player in the viral attachment process in almost every viral disease. Viruses have incorporated an array of efficient fusion proteins on their surfaces to bind efficiently to host cell receptors. They make use of the host proteolytic enzymes to rearrange their surface protein(s) into the form which facilitates their binding to host-cell membrane proteins and subsequently, fusion. This stage of viral entry is very critical and has many therapeutic implications. The current global pandemic of COVID-19 has sparked severe health crisis and economic shutdowns. SARS-CoV2, the etiological agent of the disease has led to millions of deaths and brought the scientific community together in an attempt to understand the mechanisms of SARS-CoV2 pathogenesis and mortality. Like other viral fusion machinery, CoV2 spike (S) glycoprotein- The Demogorgon poses the same questions about viral-host cell fusion. The intermediate stages of S protein-mediated viral fusion are unclear owing to the lack of structural insights and concrete biochemical evidence. The mechanism of conformational transition is still unclear. S protein binding and fusion with host cell receptors, Eg., angiotensin-converting enzyme-2 (ACE2) is accompanied by cleavage of S1/S2 subunits. To track the key events of viral-host cell fusion, we have identified (in silico) that low pH-induced conformational change and ACE-2 binding events promote S1 dissociation. Deciphering key mechanistic insights of SARS-CoV2 fusion will further our understanding of other class-I fusion proteins

bioinformatics↗