Direct correlation analysis improves fold recognition.

The extraction of correlated mutations through the method of direct information (DI) provides predicted contact residue pairs that can be used to constrain the three dimensional structures of proteins. We apply this method to a large set of decoy protein folds consisting of many thousand well-constructed models, only tens of which have the correct fold. We find that DI is able to greatly improve the ranking of the true (native) fold but others still remain high scoring that would be difficult to discard due to small shifts in the core beta sheets.

De novo backbone scaffolds for protein design.

In recent years, there have been significant advances in the field of computational protein design including the successful computational design of enzymes based on backbone scaffolds from experimentally solved structures. It is likely that large-scale sampling of protein backbone conformations will become necessary as further progress is made on more complicated systems. Removing the constraint of having to use scaffolds based on known protein backbones is a potential method of solving the problem.

Sampling of near-native protein conformations during protein structure refinement using a coarse-grained model, normal modes, and molecular dynamics simulations.

Protein structure refinement from comparative models with the goal of predicting structures at near-experimental accuracy remains an unsolved problem. Structure refinement might be achieved with an iterative protocol where the most native-like structure from a set of decoys generated from an initial model in one cycle is used as the starting structure for the next cycle. Conformational sampling based on the coarse-grained SICHO model, atomic level of detail molecular dynamics simulations, and normal-mode analysis is compared in the context of such a protocol.

Simple physics-based analytical formulas for the potentials of mean force for the interaction of amino acid side chains in water. 2. Tests with simple spherical systems.

Simple analytical functions consisting of electrostatic, polarization, Lennard-Jones or modified Lennard-Jones, and cavity terms are proposed to express the potentials of mean force analytically for spherical particles interacting in water. The cavity term was expressed either through the molecular-surface area of the solute or by using the Gaussian-overlap model of hydrophobic hydration developed in paper 1 of this series. The analytical expressions were fitted to the potentials of mean force of a methane homodimer, heterodimers composed of a methane molecule, and an ammonium cation or a chloride anion, respectively, and dimers consisting of two chloride anions, two ammonium cations, or a chloride ion and an ammonium cation.