Molecular Dynamics Simulations Provide Insight into the Structure and Stability of an Aptamer-Target System

Aptamers are single-stranded nucleic acids that behave similarly to antibodies in that they bind to certain target molecules. There are several key differences between aptamers and antibodies that make aptamers interesting molecules to model. The most important difference is that aptamers have tunable properties and are generally more chemically resistant than antibodies.^[1] As a result, we can study how the structure and stability of an aptamer can be affected by changing conditions such as pH, temperature, and concentration of aptamer. Studying a specific aptamer in lab requires time and resources. This resource requirement becomes magnified when one wishes to study a library of aptamers. A complementary method for investigation of aptamer-target systems is molecular dynamics simulations. This computational method involves taking the molecule of interest and running a simulation to create a model that gives a prediction of how the molecule will behave in real life. Our chosen aptamer is the malachite green aptamer (MGA) which binds to its target molecule: malachite green (MG). malachite green is an organic molecule mainly used in dyes and fungicides. We focus on using molecular dynamics simulations to generate updated models of how MGA behaves in water in the unbound state and while bound to malachite green. Specifically, it is of interest to determine the mechanism through which MGA binds to malachite green. It has been reported in previous studies that an “induced fit”^[2] method is the main way MGA binds to MG. In other words, the structure of MGA is only loosely determined before binding and undergoes a reorganization of structure while it is binding to MG. This raises questions about the overall flexibility and stability changes of MGA after it has bound MG. These changes can lead to a more exposed MG within the binding pocket, leaving it more susceptible to structural attacks. This is significant because the overall behavior of the MGA-MG system can change, such as faster oxidation, color change, and limited or increased fluorescence. In this presentation, we provide an additional insight into the MGA-MG system.