Molecular Simulation

At Silicon Therapeutics, we simulate biological molecules using the laws of physics. This approach allows us to predict interactions, energies and the conformational behavior of our drug discovery targets.

We go beyond binding, simulating the dynamic behavior of protein-ligand interactions to reveal how conformational changes drive biological activity and how that activity can be modulated with small molecules. Biophysics, biology and medicinal chemistry are integrated to focus our simulation efforts on the problems directly relevant to our drug discovery efforts. This leads to a richer understanding of the relationship between protein conformations and biological outcomes, enabling us to design drug molecules atom-by-atom for challenging drug targets that have previously been considered “undruggable.”

Uncovering Conformational Behavior

Professor Richard Feynman, visionary and Nobel Prize winner in physics, provided insights to understand biology at an atomic and sub-atomic level. As Professor Feynman said:

“If we were to name the most powerful assumption of all, which leads one on and on in an attempt to understand life, it is that all things are made of atoms, and that everything that living things do can be understood in terms of the jigglings and wigglings of atoms.”

At Silicon Therapeutics, our simulation platform allows us to predict the jiggling and wiggling of atoms in a biological system. However, predicting that motion alone does not tell us about the fundamental free energy landscape of the system and how it can be modulated with potential drug molecules to therapeutically alter a disease. Fortunately, when we take all of that information from the jiggling wiggling and apply statistical thermodynamics, we are able to compute both entropy (the unavailability of thermal energy for conversion into mechanical work) and enthalpy (the total heat content of the system) and apply our insights to the delicate balance of human biology by designing small molecules atom-by-atom.

Beyond Binding

Our molecular dynamics simulations lead Silicon Therapeutics scientists to develop conformational hypotheses at an atomic scale which inform our screening, design and analyses. This process is like the work of building architects who require immersive 3D computer-aided design to assess structural requirements and model how the building will function.

Our analysis features the rigorous evaluation of structural data gleaned through simulations of proteins in motion. We then design molecules atom-by-atom, prioritized for synthesis to enter our in-house laboratory for testing. We continually compile data through a combination of simulations and experiments as we drive our programs toward the clinic.

As this process progresses, we gain critical insights into a molecule’s mechanism of action. Ultimately, our cross-functional teams advance potential drug candidates to address previously undruggable protein targets with the goal of delivering novel therapeutics to treat patients.