Biophysical Society Conference | Tahoe 2022

Molecular Biophysics of Membranes

Poster Abstracts

4-POS Board 1 RANDOM-WALK MODEL OF COTRANSPORT Yan B. Barreto 1 ; Adriano M Alencar 1 ; 1 University of São Paulo (USP), Institute of Physics, São Paulo, Brazil

Cotransporters are transmembrane carrier proteins that facilitate the movement of nutrients, ions, drugs and waste across the cell membrane. In this work, we present a statistical mechanical model for the dynamics of these carrier proteins. Our starting point was the alternating-access model, which suggests the existence of six states for the cotransport cycle. Then we determined the transition probability matrix between these states and used it to write a set of master equations for describing the time evolution of the system. The asymptotic behavior of this set of equations is in agreement with the equilibrium condition obtained by other authors from thermodynamics. Next, the predictions of our model were compared with the experimental data for the lactose-H + symport catalyzed by LacY. In addition to satisfactorily describing the time course of lactose transport, we paved the way to solve an open question related to this symporter. We discovered that the importance of protonation is in the fact that the H + binding causes a large free-energy drop, reducing the rate of reverse protonation, and allowing relatively slow lactose binding to occur. In future works, our model can be used to study the mechanosensitivity of cotransporters, which is a poorly studied problem on the interface between physics and biology with possible applications to heart disease therapies.

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