Geometric characterization of the HSV - 1 glycoprotein B - amyloid β interaction in Alzheimer's disease using Forman-Ricci curvature

Alzheimer's disease involves the buildup and clumping of amyloid-beta (Aβ) molecules, but the specific ways environmental and infectious elements impact Aβ conformation are not fully understood. Herpes simplex virus type 1 (HSV-1) has been suggested as a possible factor in Alzheimer's, and interactions between the virus's glycoprotein B (gB) and Aβ might affect the peptide's structure.

Molecular dynamics (MD) simulations provide detailed atomic-level insights into these interactions, yet traditional structural indicators might not fully represent shifts in the arrangement of residue connections.

In this study, researchers present a new graph-geometric method using Forman-Ricci curvature to analyze the development of residue interaction networks during MD simulations. Each simulation frame is depicted as a residue interaction graph derived from C-C bonds, and the curvature profiles for individual residues are examined over time. The framework is tested on Aβ1-42 both by itself and when combined with HSV-1 gB.

While MD analyses reveal a stable connection between the simulated complex, favorable interaction energies, and alterations in Aβ's structure, including a shift from alpha-helical to beta-turn-rich conformations, Forman-Ricci curvature highlights significant and localized changes in the Aβ residue interaction network within the complex.

The most notable modifications are centered in the C-terminal area. These regions also show lower variability in temporal curvature and increasingly distinct geometric patterns throughout the simulation. The grouping of residues displaying coordinated curvature changes, particularly a significant C-terminal domain, is also determined through hierarchical clustering.

Overall, the findings show that Forman-Ricci curvature offers an additional way to describe the dynamics of biomolecules by capturing alterations in the spatial organization of residue interaction networks, which are not represented by standard structural descriptors. This new computational tool provides a broad method for investigating structural changes in protein molecular dynamics and offers a quantitative view of how HSV-1 gB interacting with Aβ affects its conformation.