title: Ab initio folding simulation of Trpcage by replica exchange with hybrid Hamiltonian.
abstract: Replica-exchange molecular dynamics simulations with hybrid Hamiltonian in explicit solvent were performed to study the folding of a designed 20-residue miniprotein, Trpcage, from a fully extended structure. During the simulations several folding/unfolding events happened. In the folded states the majority of experimentally observed NMR NOE restraints are satisfied. The folded structures have root mean squared deviation of 2.0 A with respect to the NMR structures considering all heavy atoms. The free-energy surface constructed by the hybrid Hamiltonian simulations is similar to the one built by a standard replica-exchange simulation which started from the native structure. Consistent with previous experimental observation, a pre-existing hydrophobic collapse in the unfolded state is detected by investigating the desolvation behavior of Trpcage. At room temperature, an intermediate state featured by a misfolded core, a nearly formed alpha-helix segment and an absence of 3(10)-helix is found. The replica exchange with hybrid Hamiltonian method is shown here to be capable of resolving the folding picture of the miniprotein.
authors.affiliation: School of Biological Sciences, Nanyang Technological University, Singapore 637551, Singapore.
authors.forename: Weixin
authors.initials: W
authors.lastname: Xu
authors.forename: Yuguang
authors.initials: Y
authors.lastname: Mu
mesh_terms: D002942:Circular Dichroism; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D010455:Peptides / Q000737:chemistry*; D017510:Protein Folding; D017433:Protein Structure, Secondary; D055672:Static Electricity; D013816:Thermodynamics; D044366:Transition Temperature; D014867:Water / Q000737:chemistry
chemical_list: D010455:Peptides; D014867:Water