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Myeloperoxidase (MPO) is a heme peroxidase with microbicidal properties. MPO plays a role in the host’s innate immunity by producing reactive oxygen species inside the cell against foreign organisms. However, there is little functional evidence linking missense mutations to human diseases. We utilized in silico saturation mutagenesis to generate and analyze the effects of 10,811 potential missense mutations on MPO stability. Our results showed that ~71% of the potential missense mutations destabilize MPO, and ~8% stabilize the MPO protein. We showed that G402W, G402Y, G361W, G402F, and G655Y would have the highest destabilizing effect on MPO. Meanwhile, D264L, G501M, D264H, D264M, and G501L have the highest stabilization effect on the MPO protein. Our computational tool prediction showed the destabilizing effects in 13 out of 14 MPO missense mutations that cause diseases in humans. We also analyzed putative post-translational modification (PTM) sites on the MPO protein and mapped the PTM sites to disease-associated missense mutations for further analysis. Our analysis showed that R327H associated with frontotemporal dementia and R548W causing generalized pustular psoriasis are near these PTM sites. Our results will aid further research into MPO as a biomarker for human complex diseases and a candidate for drug target discovery. 

This paper addresses the problem of generating coverage paths-that is, paths that pass within some sensor footprint of every point in an environment-for vehicles with Dubins motion constraints. We extend previous work that solves this coverage problem as a traveling salesman problem (TSP) by introducing a practical heuristic algorithm to reduce runtime while maintaining near-optimal path length. Furthermore, we show that generating an optimal coverage path is NP-hard by reducing from the Exact Cover problem, which provides justification for our algorithm's conversion of Dubins coverage instances to TSP instances. Extensive experiments demonstrate that the algorithm does indeed produce length paths comparable to optimal in significantly less time.