Molecular Dynamics Reveals The Mechanism Of Acetate Transport

Overview

In the microscopic arena of biology, there is a great drama of molecular transport going on all the time. Today, the main character is acetate, a molecule that plays a key role in the metabolism of living organisms. However, how acetate travels across cell membranes has always been an unsolved mystery. Now, scientists have unravelled this mystery through their keen scientific insights and advanced molecular dynamics simulations.

Background

Acetate, as a core molecule in the metabolic cycle of organisms, is not only involved in energy production and storage, but also in cell signalling and gene expression regulation. Its transport process between cells is not only related to the normal function of cells, but also key to the survival of many pathogens. However, the transport mechanism of acetate has not been fully understood, which limits our development of relevant drugs and optimisation of disease treatment strategies.

Figure 1. Acetate channel protein

Methods

The study used microsecond-level molecular dynamics simulations, a method that can simulate molecular motion at the atomic level. Combined with the umbrella sampling technique, it allows researchers to take a more detailed look at the system within a specific energy window. With this approach, the team constructed a model of acetate transport in the SatP channel and were able to capture the process by cleverly using an external electric field to accelerate the transport of acetate during the simulation. The use of this method not only improves the efficiency of the study, but also provides us with a new perspective to observe and understand the molecular transport mechanism.

 Discussion

A team of young scientists, led by Prof Suwen Zhao from iHuman Research Institute of Shanghai University of Science and Technology (SUST), finally published their research results in Journal of Chemical Information and Modelling after a long period of hard work and exploration. They not only observed the detailed process of acetate in passing through the SatP channel, but also discovered the important role of water molecules in this process, as well as the key roles of the key residues Gln50 and Phe17 in the opening of the channel.

Figure 2. Pore size and shape of acetate channel proteins under different conditions.

Acetate passage through SatP channels is always accompanied by water molecules, which form a hydrated environment in the channels and provide the necessary conditions for acetate transport. This finding suggests that water molecules may play a lubricating and guiding role in the molecular transport process.

Figure 3. Comparison of crystal structure and structure at the highest point of PMF.

In the middle of the channel, there is a narrow site formed by residues Phe17, Tyr72, and Leu131, and this narrow site opens temporarily during acetate transport, allowing acetate to pass through. This finding reveals the dynamic properties of the channel and the gating mechanism during transport.

Figure 4. Mean force potential (PMF) profiles of acetate through SatP channels.

Through the umbrella sampling technique, the team found an energy barrier of up to 15 kcal/mol, which explains why acetate transport is difficult to observe in its natural state. This finding is important for understanding the kinetic process of molecular transport and designing drug intervention strategies.

Figure 5. Structural changes of the acetate channel SatP in the open state.

 Conclusions

As this research progresses, we are gaining a deeper understanding of the microcosm of life. The revelation of the transport mechanism of acetate is not only a great step forward in science, but also a bright light on the road to human health. We expect this study to bring new insights and impetus to the future development of medicine.

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