The cs ligand binds to seven amino acids of e protein by ten hydrogen bonds see table 3. Symmdock prediction of complexes with c n symmetry. Mode of interaction of the complexes with dna protein has also been supported by molecular docking. If one looks at the crystal structures of protein dna complexes in the pdb, then this direct readout mechanism is involved in practically all the cases of specific binding. We present a proteindna docking benchmark containing 47 unboundunbound test cases of which are classified as easy, 22 as intermediate and 12 as difficult cases. Hex has been available for about 12 years now, but as far as i know, it is still the only docking and superpostion program to use. Rna protein complexes in the protein data bank were decomposed into small peptideoligonucleotide interacting fragment pairs and used as building blocks to assemble big scaffolds representing complex rna protein interactions. Pdf interfacial water molecules play an important role in many aspects of proteindna specificity and recognition. This protein structure and a database of potential ligands serve as inputs to a docking program. Fiberdock flexible backbone and sidechain refinement and re.
The docking of cs molecules in the e protein of dengue virus resulted in the interaction with the interface of domain i and ii of the protein see figure 6. The antiproliferative activity, morphological changes, and apoptosis have been evaluated by mtt assay, acridine orangeethidium bromide aoetbr fluorescence staining, and dna ladder assay. Geometric docking algorithms based on the assumption of shape complementarity between the participating molecules. Computational prediction of protein rna complex structures includes two steps. If youre lucky, its written generally enough such that it will dock a dna chain as well as a protein one. A better bet would likely be the protein protein docking code. These results demonstrate that protein dna docking is also challenging, but generally easier than for protein rna docking, perhaps because of the more limited conformational changes in typical dna structures.
Because the experimental determination of these complexes is timeconsuming and perhaps futile in some instances, we have focused on computational docking methods starting from the. Although much improvement has been made in the field of protein protein docking, in the case of protein dna complexes, however, progress lags behind. Protein receptorligand motifs fit together tightly, and are often referred to as a lock and key mechanism. How to study proteinligand interaction through molecular. The docking process is fast and consumes about 1020 min for a docking run. We present a new coarsegrained force field suitable for proteindna docking. The benchmark contains 47 unboundunbound test cases of a varying degree of difficulty. Attendees will be introduced to molecular docking technology and will have an opportunity to.
The docking protein is then phosphorylated on multiple tyrosine residues, leading to the recruitment of speci. Proteinrna docking using icm journal of chemical theory. The dataset for protein dna docking was taken from the protein dna docking benchmark created by the bonvin group. Hex can also calculate protein ligand docking, assuming the ligand is rigid, and it can superpose pairs of molecules using only knowledge of their 3d shapes. Dna ligand docking is an allatom energy based monte carlo dna ligand docking, implemented in a fully automated, parallel processing mode which predicts the binding mode of the nonmetallo ligand in the minor groove of dna. To automatically make use of the binding information from the pdb in dock ing, here we have presented hdock, a novel web server of our. I know important residues of the protein, involved in interaction but which part of dna is important is. The results of two blind trials of protein docking are encouraging for complexes that are. Thirumal kumar, in advances in protein chemistry and structural biology, 2014. Dot performs a systematic, rigidbody search of one molecule translated and rotated about a second molecule. The variety in test cases make this nonredundant benchmark a useful tool for comparison and further development of protein dna docking. Docking and scoring incorporating a model of hydrophobic enclosure for protein. As of december 2015, there have been over 40,000 downloads.
Swissdock the online docking web server of the swiss. Usually the structure has been determined using a biophysical technique such as xray crystallography or nmr spectroscopy, but can also derive from homology modeling construction. For protein dna docking, we assessed the use of a combined meta potential k. In order to avoid securityrelated warning messages when switching to secured connection, you may want either to. Protein rna and protein dna interactions play fundamental roles in many biological processes. Hex understands protein and dna structures in pdb format, and it can also read smallmolecule sdf files. Mainly because the ligand docking code tends to assume that whats being docked is a single residue. Proteinassisted rna fragment docking rnax for modeling.
Protein protein and protein dna rna docking based on a hybrid algorithm of templatebased modeling and ab initio free docking. The protein dna benchmark biomolecular docking aims at predicting the structure of a complex given the three dimensional structures of its components. While some of the existing protein protein docking methods, such as haddock 1, can handle nucleic acids, very few algorithms specifically developed 2for protein dna docking have beenreported so far 2. Pdf we present a proteindna docking benchmark containing 47 unbound unbound test cases of which are classified as easy, 22 as intermediate and 12. Regardless, bound docking usually means the initial structures come from the structure of the complex, usually experimentally determined.
Firedock refinement and rescoring of rigidbody protein protein docking solutions. Dot is a software package for docking macromolecules, including proteins, dna, and rna. Results indicate hundreds of druglike and leadlike ligands. In this case, the bound structure is used for unbound docking. One possible application of the docking module yasara dock is the prediction of these specific protein dna interactions. Further details can be found in the supplementary results. This method has already been successful for designing dna protein and protein protein interfaces. Docking rigid, symmetric, protein protein, protein drug, protein dna, protein peptide patchdock rigid unbound docking of molecules. Dnaprotein binding, molecular docking, and in vitro.
Protein docking is used to check the structure, position and orientation of a protein when it interacts with small molecules like ligands. Determining the complex structures of these interactions is valuable, in which molecular docking has played an important role. Computational methods such as docking have been developed to complement existing biophysical and structural biology techniques. Performance of the npdock server for protein dna complexes. Bonvin 0 0 bijvoet center for biomolecular research, science faculty, utrecht university, the netherlands we present a protein dna docking benchmark containing 47 unboundunbound test cases of which are classified as. Protein rna interactions play an important role in many biological processes.
It combines 1 gramm for global macromolecular docking, 2 scoring with a statistical potential, 3 clustering of bestscored structures, and 4 local refinement. To perform a docking screen, the first requirement is a structure of the protein of interest. Macromolecular docking is the computational modelling of the quaternary structure of complexes formed by two or more interacting biological macromolecules. Hex is an interactive protein docking and molecular superposition program, written by dave ritchie. Hydrogen donoracceptor complementarity protein drug. Protein protein and protein dna rna interactions play a fundamental role in a variety of biological processes. Which software should be used to do dna protein docking. Predictive docking of protein protein and protein dna complexes. Mycobacterium tuberculosis is a gram positive, acidfast bacteria belonging to genus mycobacterium, is the leading causative agent of most cases of tuberculosis.
Swissdock, a free protein ligand docking web service powered by eadock dss by the molecular modeling group of the swiss institute of bioinformatics. Moreover, hdock also supports proteinrnadna docking with an intrinsic. Several methods for proteinprotein docking have been developed and. Proteinprotein and protein ligand docking bioinfo3d.
A detailed understanding of these interactions requires knowledge about protein nucleic acid complex structures. The pathogenicity of the bacteria is enhanced by its developed dna repair mechanism. For two proteins, the docking problem is very difficult since the search space all possible relative conformations is extremely large in the case of a small molecule drug, peptide or ligand binding to a protein, we have a chance of exploring the conformational space, at least for. Molecular surface complementarity protein protein, protein ligand, protein drug. Given the 3d structures of two molecules, determine the best binding modes. Docking was performed for unique lists of dna repair proteins which predict os for aml, cancers of the breast, lung, colon, and ovaries, gbm, melanoma, and renal papillary cancer. Molecular docking studies this chapter discusses about the molecular docking studies of the. This yielded a total of 23 test cases supplementary table s2. Proteinprotein and proteinligand docking intechopen. Strategies for protein protein docking evaluation of the results of docking simulations. Pdf homology modeling, molecular docking and dna binding. Docking molecular an overview sciencedirect topics.
Home software benchmark performance decoys zlab docking sites references. Molecular docking is also referred to as small molecular docking. Tested on the cases with weakly homologous complexes of docking benchmarks, the hdock pipeline tied with templatebased modeling on the protein protein and protein dna benchmarks and performed better than templatebased modeling on the. Bujnicki, details to be published elsewhere that comprises quasidnp, the dfire potential and a potential developed by varani et al. Which software should be used to do dnaprotein docking. The paradock algorithm contains four main stages illustrated in figure 2. For the second method, we used a dna protein rigid docking method to compare the dna binding pattern of. Proteindna docking with a coarsegrained force field bmc. These configurations are evaluated using scoring functions to distinguish. Npdock nucleic acid protein dock is a web server for modeling of rna protein and dna protein complex structures.