The Computational Microscope

University Of Illinois At Urbana-Champaign, Urbana IL

Investigators

Abstract

Cells are the building blocks of life, yet they are themselves a collection of proteins, small molecules, and solvent, none of which are, in and of themselves, alive. How living things can arise from the "behavior" of molecules, which are simply obeying the laws of physics, is the essential conundrum of modern biology. The rise of scientific supercomputing has offered the chance to study living systems at the levels of atoms, cells, and all levels in between.  With Blue Waters, it is now possible to take the most critical step from inanimate to animate matter by describing assembly and cooperation of thousands of macromolecules made of billions of atoms.  The ability to explore living systems via the "computational microscope" of molecular dynamics simulations has a profound impact not only on the progress of basic science, but also in the treatment of disease and the development of drugs. This project will use Blue Waters to study three types of biomolecular systems: the microtubules that make up the cell's cytoskeleton, the chemosensory array that acts as a "bacterial brain", and two highly relevant retroviruses: HIV (human immunodeficiency virus) and RSV (Rous sarcoma virus).  The first project will model microtubules, in their native form, as well as the interactions between the microtubule, its regulatory partners, and anti-cancer agents. Simulations of the microtubule and its interactions with drugs can help drive the development of new microtubule-attacking cancer therapies.  The HIV part of the virus project builds on prior success in modeling the full HIV capsid to evaluate the effects of HIV drugs on capsid stability and to model the essential interactions between the capsid and host cell factors. Simulations of the HIV capsid provide the necessary detailed knowledge of the vital infection process to develop new HIV therapies.  The RSV part of the virus project has constructed the first model of an intermediate stage in virus capsid maturation, which will be used to describe the maturation process of retroviruses may open the doors to a new type of anti-viral drug which attacks that maturation process.  The chemosensory array project seeks to answer how input from many chemical sensors on the bacterial surface are transduced across hundreds of nanometers in the array, leading the cell to decide if it should continue swimming or change direction, to adapt to changing environments.  The chemosensory array is a universal structure in bacteria, but absent in eukaryotes, offering a new target for antibiotic drugs - a desperately needed advancement in combating bacterial resistance to current antibiotics. Each of the projects proposed presents an opportunity for petascale computing to contribute to mankind?s health and to answer one of mankind's oldest questions: "What is life?"