Research

Perspective

Proteins are the molecular unit at the origin of the fascinating biochemical circuitry of cells. Several processes fundamental to life: transcription, translation, communications, and responses to external stimuli, all rely on nanomachines consisting of protein catalysts, switches, and transducers. To carry out their biological function, proteins undergo structural changes on multiple spatial and time scales. The recent transformational advances in artificial intelligence and machine learning technologies (hereafter collectively referred to as AI) are ushering in a new dawn of four dimensional structural biology (dynamics being the fourth dimension). The release of AlphaFold2 (AF2) and other AI structure prediction methods have galvanized protein scientists – witness the avalanche of publications and preprints and the constant stream of algorithms that harness the power of these approaches.

The Center harnesses this revolution by integrating AI methods and experimentation to reveal modes of protein dynamics, leveraging this knowledge to build novel proteins with designer dynamics for in silico drug screening and decoding how mutations lead to disease phenotype. Vanderbilt University researchers are world renowned for their contributions to:

• Illuminating dynamics—using both experimental approaches and recently AI-AlphaFold2 methods—for proteins involved in drug resistance, neurotransmitter transport, and cancer.
• Developing and applying modern cheminformatics tools to catapult how quantitative structure-activity relationship modeling is used to discover new small molecule modulators of proteins responsible for progression of cancer, obesity, heart disease, neurodegenerative diseases, diabetes, and more.
• Pioneering the use of DNA databases to uncover how mutations lead to disease phenotypes.