title: Protein Folding and Structure Prediction from the Ground Up II: AAWSEM for α/β Proteins.
abstract: The atomistic associative memory, water mediated, structure and energy model (AAWSEM) is an efficient coarse-grained force field with transferable tertiary interactions that incorporates local in sequence energetic biases using structural information derived from all-atom simulations of long segments of the protein. For α helical proteins, the accuracy of structure prediction using AAWSEM has been established previously. In this article, we examine the capability of AAWSEM to predict the structure of α/β proteins. We also elaborate on an iterative approach that uses the structures from a first round of AAWSEM simulation as fragment memories. This iterative scheme improves the quality of the structure prediction and makes the free energy profile more funneled toward native configurations. We explore the use of clustering analyses as a way of evaluating the confidence in various structure prediction models. Clustering using a local relative order parameter (mutual Q) of the predicted structural ensemble turns out to be optimal. The tightest cluster according to mutual Q generally has the most correctly folded structure. Since there is no bioinformatic input, AAWSEM amounts to an ab initio protein structure prediction method that combines the efficiency of coarse-grained simulations with the local structural accuracy that can be achieved from all-atom simulations.
authors: Center for Theoretical Biological Physics, Rice University , 6100 Main St., Houston, Texas 77005-1892, United States.|Department of Bioengineering, Rice University , 6100 Main St., Houston, Texas 77005-1892, United States.
authors: Mingchen
authors: M
authors: Chen
authors: Center for Theoretical Biological Physics, Rice University , 6100 Main St., Houston, Texas 77005-1892, United States.|Department of Physics and Astronomy, Rice University , 6100 Main St., Houston, Texas 77005-1892, United States.
authors: Xingcheng
authors: X
authors: Lin
authors: Center for Theoretical Biological Physics, Rice University , 6100 Main St., Houston, Texas 77005-1892, United States.|Department of Physics and Astronomy, Rice University , 6100 Main St., Houston, Texas 77005-1892, United States.
authors: Wei
authors: W
authors: Lu
authors: Center for Theoretical Biological Physics, Rice University , 6100 Main St., Houston, Texas 77005-1892, United States.|Department of Physics and Astronomy, Rice University , 6100 Main St., Houston, Texas 77005-1892, United States.|Department of Chemistry, Rice University , 6100 Main St., Houston, Texas 77005-1892, United States.|Department of Biosciences, Rice University , 6100 Main St., Houston, Texas 77005-1892, United States.
authors: José N
authors: JN
authors: Onuchic
authors: Center for Theoretical Biological Physics, Rice University , 6100 Main St., Houston, Texas 77005-1892, United States.|Department of Physics and Astronomy, Rice University , 6100 Main St., Houston, Texas 77005-1892, United States.|Department of Chemistry, Rice University , 6100 Main St., Houston, Texas 77005-1892, United States.|Department of Biosciences, Rice University , 6100 Main St., Houston, Texas 77005-1892, United States.
authors: Peter G
authors: PG
authors: Wolynes
mesh_terms: D056004:Molecular Dynamics Simulation; D011487:Protein Conformation; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D011506:Proteins