The availability of an abundance of experimentally determined structures of proteins and protein-protein complexes is fueling research on protein interactions and complex formation.
Innovative approaches investigating these interactions at the molecular level are offering new insights into drug discovery and design.
Researchers are scheduled to present the cutting edge of their tools and technologies targeting protein-protein interactions (PPIs) at Select Biosciences’ upcoming “Discovery Chemistry Congress” meeting.
New tools and approaches aimed at visualization, interaction, and software development facilitate the understanding of the complex nature of protein interactions, especially in the context of cellular environments, according to Arthur Olson, Ph.D., professor at the Scripps Research Institute.
“The software takes the recipe of all the proteins in a cellular environment and uses that information to build a 3D physical model of that environment,” he explains. By modifying the ingredients in the external recipe, researchers can study specific interactions more readily, according to Dr. Olson.
The Molecular Graphics Laboratory under the direction of Dr. Olson has developed novel techniques for computation analysis and modeling of the interaction of protein-ligand, protein-protein, and other biomolecular systems. Understanding drug resistance in HIV is one of his goals.
Using high-end computer graphics such as those developed for gaming and animation in Hollywood, Dr. Olson’s team has designed molecular modeling software to visualize protein interactions. His work on the ongoing HIV project takes the virus and its interactions as a whole that cannot be known from their individual binary PPIs. In his view, “the ability to model crowded environments in cells and viruses is critical to develop tools for designing drugs.”
His lab at the Scripps Institute is engaged in developing tools to build a better model of the cellular environment so scientists and others can develop a realistic simulation of living systems. “As we continue to stabilize and make the algorithms deeper and broader to make them useful for research, we can apply them as useful tools for scientists to communicate with each other in publications, to teach, or for public outreach projects.”
Indeed, Dr. Olson and his team are credited with the development of AutoDock, a suite of automated docking tools, designed to predict how small molecules, such as substrates or drug candidates, bind to a receptor of known 3D structure. It is used by more than 29,000 researchers around the world, he says.
The protein-protein docking phenomenon is one of the key elements of activity in computational structural biology. Characterization of conformational properties of protein-protein interactions is essential to understanding the mechanisms of protein association, and insight into the conformations of the surface side chains is critical for modeling protein complexes.