ABSTRACT
The 84-residue homotetrameric BBAT1 is one of the smallest stable protein complexes and therefore is a good test system to study the self-assembly of multimeric proteins. We have researched for this protein the interplay between the folding of monomers and their assembly into tetramers. Replica exchange molecular dynamics simulations relying on a Go model are compared with earlier simulations that use the physics-based coarse-grained UNRES model.
Subject(s)
Models, Chemical , Models, Molecular , Protein Folding , Proteins/chemistry , Proteins/ultrastructure , Computer Simulation , Protein ConformationABSTRACT
We describe optimized parallel tempering simulations of the 46-residue B-fragment of protein A. Native-like configurations with a root-mean-square deviation of approximately 3 A to the experimentally determined structure (Protein Data Bank identifier 1BDD) are found. However, at biologically relevant temperatures such conformations appear with only approximately 10 % frequency in our simulations. Possible shortcomings in our energy function are discussed.
Subject(s)
Computer Simulation , Models, Molecular , Protein Folding , Staphylococcal Protein A/chemistry , Databases, Protein , Protein Structure, Secondary , Rotation , Temperature , ThermodynamicsABSTRACT
We present a Monte Carlo algorithm that facilitates efficient parallel tempering simulations of the density of states g(E) . We show that the algorithm eliminates the supercritical slowing down in the case of the Q=20 and Q=256 Potts models in two dimensions, typical examples for systems with extreme first-order phase transitions. As recently predicted, and shown here, the microcanonical heat capacity along the calorimetric curve has negative values for finite systems.
ABSTRACT
Experimentally well-characterized proteins that are small enough to be computationally tractable provide useful information for refining existing all-atom force fields. This is used by us for reparametrizing a recently developed all-atom force field. Relying on high statistics parallel tempering simulations of a designed 20 residue beta-sheet peptide, we propose incremental changes that improve the force field's range of applicability.
Subject(s)
Models, Chemical , Models, Molecular , Proteins/chemistry , Proteins/ultrastructure , Computer Simulation , Protein Conformation , Protein Folding , Stress, MechanicalABSTRACT
Using the 28 residue betabetaalpha protein FSD-EY as a target system, we examine correction terms for the ECEPP/3 force field. We find an increased probability of formation of the native state at low temperatures resulting from a reduced propensity to form alpha helices and increased formation of beta sheets. Our analysis of the observed folding events suggests that the C-terminal helix of FSD-EY is much more stable than the N-terminal beta hairpin and forms first. The hydrophobic groups of the helix provide a template which promotes the formation of the beta hairpin that is never observed to form without the helix.
