10,122 research outputs found
RosettaBackrub--a web server for flexible backbone protein structure modeling and design.
The RosettaBackrub server (http://kortemmelab.ucsf.edu/backrub) implements the Backrub method, derived from observations of alternative conformations in high-resolution protein crystal structures, for flexible backbone protein modeling. Backrub modeling is applied to three related applications using the Rosetta program for structure prediction and design: (I) modeling of structures of point mutations, (II) generating protein conformational ensembles and designing sequences consistent with these conformations and (III) predicting tolerated sequences at protein-protein interfaces. The three protocols have been validated on experimental data. Starting from a user-provided single input protein structure in PDB format, the server generates near-native conformational ensembles. The predicted conformations and sequences can be used for different applications, such as to guide mutagenesis experiments, for ensemble-docking approaches or to generate sequence libraries for protein design
Open Boundary Simulations of Proteins and Their Hydration Shells by Hamiltonian Adaptive Resolution Scheme
The recently proposed Hamiltonian Adaptive Resolution Scheme (H-AdResS)
allows to perform molecular simulations in an open boundary framework. It
allows to change on the fly the resolution of specific subset of molecules
(usually the solvent), which are free to diffuse between the atomistic region
and the coarse-grained reservoir. So far, the method has been successfully
applied to pure liquids. Coupling the H-AdResS methodology to hybrid models of
proteins, such as the Molecular Mechanics/Coarse-Grained (MM/CG) scheme, is a
promising approach for rigorous calculations of ligand binding free energies in
low-resolution protein models. Towards this goal, here we apply for the first
time H-AdResS to two atomistic proteins in dual-resolution solvent, proving its
ability to reproduce structural and dynamic properties of both the proteins and
the solvent, as obtained from atomistic simulations.Comment: This document is the Accepted Manuscript version of a Published Work
that appeared in final form in Journal of Chemical Theory and Computation,
copyright \c{opyright} American Chemical Society after peer review and
technical editing by the publishe
CLP-based protein fragment assembly
The paper investigates a novel approach, based on Constraint Logic
Programming (CLP), to predict the 3D conformation of a protein via fragments
assembly. The fragments are extracted by a preprocessor-also developed for this
work- from a database of known protein structures that clusters and classifies
the fragments according to similarity and frequency. The problem of assembling
fragments into a complete conformation is mapped to a constraint solving
problem and solved using CLP. The constraint-based model uses a medium
discretization degree Ca-side chain centroid protein model that offers
efficiency and a good approximation for space filling. The approach adapts
existing energy models to the protein representation used and applies a large
neighboring search strategy. The results shows the feasibility and efficiency
of the method. The declarative nature of the solution allows to include future
extensions, e.g., different size fragments for better accuracy.Comment: special issue dedicated to ICLP 201
Loop-closure principles in protein folding
Simple theoretical concepts and models have been helpful to understand the
folding rates and routes of single-domain proteins. As reviewed in this
article, a physical principle that appears to underly these models is loop
closure.Comment: 27 pages, 5 figures; to appear in Archives of Biochemistry and
Biophysic
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