| Classical molecular dynamics simulation is a generally applicable method for the study of biomolecular aggregates of proteins, lipids, and nucleic acids. As experimental techniques have revealed the structures of larger and more complex biomolecular machines, the time required to complete even a single meaningful simulation of such systems has become prohibitive. We have developed the program NAMD to simulate systems of 50,000–500,000 atoms efficiently with full electrostatics on parallel computers with 1000 and more processors. NAMD's scalability is achieved through latency tolerant adaptive message-driven execution and measurement-based load balancing. NAMD is implemented in C++ and uses object-oriented design and threads to shield the basic algorithms from the necessary complexity of high-performance parallel execution. Apolipoprotein A-I is the primary protein constituent of high density lipoprotein particles, which transport cholesterol in the bloodstream. In collaboration with A. Jonas, we have constructed and simulated models of the nascent discoidal form of these particles, providing theoretical insight to the debate regarding the lipid-bound structure of the protein. Recently, S. Sligar and coworkers have created 10 nm phospholipid bilayer nanoparticles comprising a small lipid bilayer disk solubilized by synthetic membrane scaffold proteins derived from apolipoprotein A-I. Membrane proteins may be embedded in the water-soluble disks, with various medical and technological applications. We are working to develop variant scaffold proteins that produce disks of greater size, stability, and homogeneity. Our simulations have demonstrated a significant deviation from idealized cylindrical structure, and are being used in the interpretation of small angle x-ray scattering data. |
