title: A Hybrid Monte Carlo Scheme for Multibackbone Protein Design.
abstract: Multistate protein design explores side chain mutations, with the backbone allowed to sample a small, predetermined library of conformations. To achieve Boltzmann sampling of sequences and conformations, we use a hybrid Monte Carlo (MC) scheme: a trial hop between backbone models is followed by a short MC segment where side chain rotamers adjust to the new backbone, before applying a Metropolis-like acceptance test. The theoretical form and a practical approximation for the acceptance test are derived. We then compute backbone conformational free energies for two SH2 and SH3 proteins using different routes and protocols, and verify that for simple test problems, the free energy behaves like a state function, a hallmark of Boltzmann sampling.
authors: Laboratoire de Biochimie (CNRS UMR7654), Ecole Polytechnique , Palaiseau, France.|Maison de la Simulation, CEA, CNRS, Univ. Paris-Sud, UVSQ, Université Paris-Saclay , 91191 Gif-sur-Yvette, France.
authors: Karen
authors: K
authors: Druart
authors: Maison de la Simulation, CEA, CNRS, Univ. Paris-Sud, UVSQ, Université Paris-Saclay , 91191 Gif-sur-Yvette, France.
authors: Julien
authors: J
authors: Bigot
authors: Maison de la Simulation, CEA, CNRS, Univ. Paris-Sud, UVSQ, Université Paris-Saclay , 91191 Gif-sur-Yvette, France.
authors: Edouard
authors: E
authors: Audit
authors: Laboratoire de Biochimie (CNRS UMR7654), Ecole Polytechnique , Palaiseau, France.
authors: Thomas
authors: T
authors: Simonson
mesh_terms: D020134:Catalytic Domain; D004798:Enzymes / Q000737:chemistry / Q000378:metabolism; D056004:Molecular Dynamics Simulation; D009010:Monte Carlo Method; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D013816:Thermodynamics; D018909:src Homology Domains
chemical_list: D004798:Enzymes; D011506:Proteins