Project Summary / Abstract The core mission of the Center is the development of novel and enhanced technologies for the use of computa- tional and experimental biologists. Providing molecular cell biologists with the most advanced computational tools permits multidisciplinary collaborations not possible otherwise. The Center currently supports a number of such collaborations, termed here `driving biomedical projects' (DBPs), which involve leading researchers all over the world, and range from the study of viruses and bacterial molecular machines to photosynthetic organelles and even an atomistic representation of an entire minimal cell. These exceptional projects are motivating a wide range of technological developments at the Center, both practical and theoretical, to enable biomedical researchers to approach problems in ways previously impossible. The presented DBPs push computational technologies to support the investigation of ever-larger spatial and temporal scales in a wide range of biomedical problems, and can be described briefly as follows: DBP1: Viral Infection: will focus on accurately simulating virus capsids in more physiologically-realistic environments; DBP2: Symbiont Bacteria within the Human Body: will focus on the structures and mechanisms of large macromolecular complexes involved in key processes underlying bacterial interactions with humans; DBP3: Molecular Motors: will investigate the mechanics of long timescale phenomena and chemical reactions taking place within molecular motors; DBP4: Neurons and Synapses: will study the key molecular mechanisms behind neural signaling regulation processes; DBP5: Membrane Transporters: will target large-scale conformational changes that are central to the mechanism of membrane transporters. DBP6: Bioener- getic Membranes: will characterize chemical energy conversion in biological cells, requiring the first billion-atom biological simulations; DBP7: Chromatin: will probe the structural changes in chromatin brought about by epi- genetic modifications; DBP8: Bacterial & Eukaryal Systems: will explore the proliferation and differentiation of hematopoietic stem cells; DBP9: Minimal Cell: will employ genome-scale reaction-diffusion models to probe the network of key cellular processes and reactions within a minimal cell, paving the way for the first atomistic de- scription of a whole cell. These endeavors and the tools they inspire, require software that both harnesses the power of existing supercomputing facilities and anticipates the immense technological opportunities feasible on next-generation exascale hardware. Taken together, the technological advancements proposed here will help to bring about a new era in computational biology, one that bridges the gap between molecules and cells to yield a comprehensive picture of cellular life.