Biomolecules achieve large motions in the course of folding and conformational change. These motions are difficult to study with molecular dynamics (MD) due to limitations on the practical timescale of MD simulations, and for this reason are often studied with simplified approaches such as the representation of residues as beads. Geometric simulation is a method, based on rigidity analysis [1], for rapidly searching conformational space with all-atom steric detail. It can be combined with scoring functions representing long-range interactions to simulate peptide folding and aggregation; with bias vectors obtained from methods such as the elastic network model; and with biasing towards a known target conformation. We present applications of geometric simulation to folding and conformational change in proteins, and we examine in detail the mobility, folding and aggregation of prion protein (PrP) with comparison to MD and NMR data.

(1) Physical Biology 2, S127-S136 (2005)