Molecular dynamics and machine learning stratify motion-dependent activity profiles of S-layer destabilizing nanobodies.

ABSTRACT: Nanobody (Nb)-induced disassembly of surface array protein (Sap) S-layers, a two-dimensional paracrystalline protein lattice from Bacillus anthracis, has been presented as a therapeutic intervention for lethal anthrax infections. However, only a subset of existing Nbs with affinity to Sap exhibit depolymerization activity, suggesting that affinity and epitope recognition are not enough to explain inhibitory activity. In this study, we performed all-atom molecular dynamics simulations of each Nb bound to the Sap binding site and trained a collection of machine learning classifiers to predict whether each Nb induces depolymerization. We used feature importance analysis to filter out unnecessary features and engineered remaining features to regularize the feature landscape and encourag

SUBMITTER: Cecil AJ 

PROVIDER: S-EPMC11631148 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature