Geofold: topology-based protein unfolding pathways capture the effects of engineered disulfides on kinetic stability.

ABSTRACT: Protein unfolding is modeled as an ensemble of pathways, where each step in each pathway is the addition of one topologically possible conformational degree of freedom. Starting with a known protein structure, GeoFold hierarchically partitions (cuts) the native structure into substructures using revolute joints and translations. The energy of each cut and its activation barrier are calculated using buried solvent accessible surface area, side chain entropy, hydrogen bonding, buried cavities, and backbone degrees of freedom. A directed acyclic graph is constructed from the cuts, representing a network of simultaneous equilibria. Finite difference simulations on this graph simulate native unfolding pathways. Experimentally observed changes in the unfolding rates for disulfide mutants of barn

SUBMITTER: Ramakrishnan V 

PROVIDER: S-EPMC3277656 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature