(691a) Exploring the Mechanism of Mutation Induced Surfactant Protein D's Higher Antiviral Activity at the Molecular Level

Pulmonary surfactant (PS) is a vital lipid-protein mixture in the lungs that facilitates healthy breathing and defends against airborne pathogens. Four types of lipids make up 90% of pulmonary surfactant and four proteins comprise the other 10%. This study focuses on surfactant protein D (SP-D), which is one of the two large hydrophilic surfactant proteins that interact with airborne pathogens acting as a host defense in the lungs. These proteins act as our first line of defense against airborne pathogens such as bacteria, fungi, pollen, and yeast by binding glycans on the pathogen's surface and flagging them for phagocytosis.Intriguingly, two point mutations (Asp325Ala and Arg343Val) in SP-D have been shown to inhibit related airborne pathogens much more potently than wild type (WT) SP-D; however, the molecular mechanisms of the mutations' influence on SP-D's binding ability with the viral surface glycan remains unclear.In this study, we use full-atomistic molecular dynamics (MD) simulation with microsecond trajectories to explore the molecular mechanism of how Asp325Ala and Arg343Val mutations affect SP-D's ability to bind viral glycans, using trimannose as a model. Utilizing computational models of SP-D and trimannose elucidates their critical structural and mechanistic properties