The FALC-Loop web server provides an online interface for protein loop modeling by employing an ab initio loop modeling method called FALC (fragment assembly and analytical loop closure). The server may be used to construct loop regions in homology modeling, to refine unreliable loop regions in experimental structures or to model segments of designed sequences. The FALC method is computationally less expensive than typical ab initio methods because the conformational search space is effectively reduced by the use of fragments derived from a structure database. The analytical loop closure algorithm allows efficient search for loop conformations that fit into the protein framework starting from the fragment-assembled structures. The FALC method shows prediction accuracy comparable to other state-of-the-art loop modeling methods. Top-ranked model structures can be visualized on the web server, and an ensemble of loop structures can be downloaded for further analysis. The web server can be freely accessed at http://falc-loop.seoklab.org/.
Most proteins function by interacting with other molecules. Their
interaction interfaces are highly conserved throughout evolution to
avoid undesirable interactions that lead to fatal disorders in cells.
Rational drug discovery includes computational methods to identify the
interaction sites of lead compounds to the target molecules. Identifying
and classifying protein interaction interfaces on a large scale can
help researchers discover drug targets more efficiently.
Description
We introduce a large-scale protein domain interaction interface database called InterPare http://interpare.netwebcite.
It contains both inter-chain (between chains) interfaces and
intra-chain (within chain) interfaces. InterPare uses three methods to
detect interfaces: 1) the geometric distance method for checking the
distance between atoms that belong to different domains, 2) Accessible
Surface Area (ASA), a method for detecting the buried region of a
protein that is detached from a solvent when forming multimers or
complexes, and 3) the Voronoi diagram, a computational geometry method
that uses a mathematical definition of interface regions. InterPare
includes visualization tools to display protein interior, surface, and
interaction interfaces. It also provides statistics such as the amino
acid propensities of queried protein according to its interior, surface,
and interface region. The atom coordinates that belong to interface,
surface, and interior regions can be downloaded from the website.
Conclusion
InterPare is an open and public database server for protein
interaction interface information. It contains the large-scale interface
data for proteins whose 3D-structures are known. As of November 2004,
there were 10,583 (Geometric distance), 10,431 (ASA), and 11,010
(Voronoi diagram) entries in the Protein Data Bank (PDB) containing
interfaces, according to the above three methods. In the case of the
geometric distance method, there are 31,620 inter-chain domain-domain
interaction interfaces and 12,758 intra-chain domain-domain interfaces.
Hahnbeom Park, Junsu Ko, Keehyoung Joo, Julian Lee, Chaok Seok*, and Jooyoung Lee*
Keywords:
protein structure prediction
protein structure refinement
protein terminus modeling
CASP
fragment assembly
Abstract
The rapid increase in the number of experimentally determined protein structures in recent years enables us to obtain more reliable protein tertiary structure models than ever by template-based modeling. However, refinement of template-based models beyond the limit available from the best templates is still needed for understanding protein function in atomic detail. In this work, we develop a new method for protein terminus modeling that can be applied to refinement of models with unreliable terminus structures. The energy function for terminus modeling consists of both physics-based and knowledge-based potential terms with carefully optimized relative weights. Effective sampling of both the framework and terminus is performed using the conformational space annealing technique. This method has been tested on a set of termini derived from a non-redundant structure database and two sets of termini from the CASP8 targets. The performance of the terminus modeling method is significantly improved over our previous method that does not employ terminus refinement. It is also comparable or superior to the best server methods tested in CASP8. The success of the current approach suggests that similar strategy may be applied to other types of refinement problems such as loop modeling or secondary structure rearrangement. Proteins 2011
