Naslov
Why Should Metformin Not Be Given in Advanced Kidney Disease? Potential Leads from Computer Simulations

Autori
Kokic Males, Visnja ; Požar, Martina

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
5th International Conference on Physics & Biological Systems 2021 / - , 2021, 44-44

Skup
5th International Conference onPhysics & Biological Systems 2021

Mjesto i datum
Online, 22.06.2021. - 25.06.2021

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
metformin ; MATE1 ; diabetes ; chronic kidney disease ; molecular dynamics ; computer simulation

Sažetak
Metformin is considered as the go-to drug in the treatment of diabetes. However, it is either prescribed in lower doses or not prescribed at all to patients with kidney problems. To find a potential explanation for this practice, we employed atomistic-level computer simulations to simulate the transport of metformin through multidrug and toxin extrusion 1 (MATE1), a protein known to play a key role in the expulsion of metformin into urine. Herein, we examine the hydrogen bonding between MATE1 and one or more metformin molecules. The simulation results indicate that metformin continuously forms and breaks off hydrogen bonds with MATE1 residues. However, the mean hydrogen bond lifetimes increase for an order of magnitude when three metformin molecules are inserted instead of one. This new insight into the metformin transport process may provide the molecular foundation behind the clinical practice of not prescribing metformin to kidney disease patients.

Izvorni jezik
Engleski

Znanstvena područja
Fizika

POVEZANOST RADA