We present a fast implementation of the nudged elastic band (NEB) method into the particle mesh Ewald molecular dynamics (pmemd) module of the Amber software package both for central processing units (CPU) and graphics processing units (GPU). The accuracy of the new implementation has been validated for three cases: a conformational change of alanine dipeptide, the α-helix to β-sheet transition in polyalanine, and a large conformational transition in human 8oxoguanine-DNA glycosylase with DNA complex (OGG1-DNA). Timing benchmark tests were performed on the explicitly solvated OGG1-DNA system containing ~50k atoms. The GPUoptimized implementation of NEB achieves more than two orders of magnitude speedup compared to the previous CPU implementation performed with a two-core CPU processor. The speed and scalable features of this implementation will enable NEB applications on larger and more complex systems.

RhoB is an early-response gene whose expression is elevated by multiple cellular stresses; this gene plays an important role in cancer, macrophage motility, and apoptosis. These factors are essential for the onset of type 1 diabetes mellitus and related complications. This study explores the role of RhoB in β-cell depletion and hyperglycemia-associated complications and tests whether the pleiotropic effect of statins on glycemic control is RhoB dependent. We induced β-cell depletion in RhoB(+/+), RhoB(+/-), and RhoB(-/-) mice with streptozotocin (STZ). Diabetic status was assessed by glucose tolerance and pancreatic islet loss. RhoB(-/-) mice showed a significant reduction in the severity of STZ-induced diabetes; only 13% of the STZ-treated RhoB-null animals became hyperglycemic, as opposed to 61% of the wild-type controls. Diabetes-related complications, such as wound healing rate and onset of nephropathy, were also assessed. Hyperglycemic RhoB(-/-) mice had fewer signs of nephropathy and showed faster wound healing than RhoB(+/+) animals. After assessing the diabetic status of mice treated simultaneously with STZ and simvastatin, we conclude that the effect of statins in improving glycemic control is RhoB independent. We propose that RhoB is a modifier of diabetes, important for the induction of β-cell loss. Suppression of RhoB expression may have potential application in the treatment of diabetes and associated complications.

We present a fast implementation of the nudged elastic band (NEB) method into the particle mesh Ewald molecular dynamics (pmemd) module of the Amber software package both for central processing units (CPU) and graphics processing units (GPU). The accuracy of the new implementation has been validated for three cases: a conformational change of alanine dipeptide, the α-helix to ß-sheet transition in polyalanine, and a large conformational transition in human 8-oxoguanine–DNA glycosylase with DNA complex (OGG1–DNA). Timing benchmark tests were performed on the explicitly solvated OGG1–DNA system containing ~50k atoms. The GPU-optimized implementation of NEB achieves more than two orders of magnitude speedup compared to the previous CPU implementation performed with a two-core CPU processor. The speed and scalable features of this implementation will enable NEB applications on larger and more complex systems.