Optimizing NAMD to visualize how membrane binding is involved in the action of neutralizing influenza antibodies

The poster reports on the optimization of our MD code, NAMD, and its use in simulating the hemagglutinin (HA) protein from the influenza virus. The model reported here for HA is the most complete representation of the protein, constructed using an array of modeling and simulation systems in the calculations. HA was then embedded in a viral membrane using an advanced simulation in which the membrane was deformed to accommodate the experimental complex between HA and its neutralizing antibody. This model showed for the first time how antibodies interact directly with the membrane. Identified membrane-interacting residues by the simulations were validated using experimental mutagenesis studies. </p

Intelligent resolution: Integrating Cryo-EM with AI-driven multi-resolution simulations to observe the severe acute respiratory syndrome coronavirus-2 replication-transcription machinery in action

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) replication transcription complex (RTC) is a multi-domain protein responsible for replicating and transcribing the viral mRNA inside a human cell. Attacking RTC function with pharmaceutical compounds is a pathway to treating COVID-19. Conventional tools, e.g. cryo-electron microscopy and all-atom molecular dynamics (AAMD), do not provide sufficiently high resolution or timescale to capture important dynamics of this molecular machine. Consequently, we develop an innovative workflow that bridges the gap between these resolutions, using mesoscale fluctuating finite element analysis (FFEA) continuum simulations and a hierarchy of AI-methods that continually learn and infer features for maintaining consistency between AAMD and FFEA simulations. We leverage a multi-site distributed workflow manager to orchestrate AI, FFEA, and AAMD jobs, providing optimal resource utilization across HPC centers. Our study provides unprecedented access to study the SARS-CoV-2 RTC machinery, while providing general capability for AI-enabled multi-resolution simulations at scale