One possible application of the docking module yasara dock is the prediction of these specific protein dna interactions. As of december 2015, there have been over 40,000 downloads. Unbound, on the other hand, means the initial structures come from structures of the same protein rna dna molecule that were determined in isolation. 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 easy, 22 as intermediate and 12 as difficult cases.
Regardless, bound docking usually means the initial structures come from the structure of the complex, usually experimentally determined. Swissdock the online docking web server of the swiss. Dot performs a systematic, rigidbody search of one molecule translated and rotated about a second molecule. 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.
Protein protein complexes are the most commonly attempted targets of such modelling, followed by protein nucleic acid complexes. Molecular surface complementarity protein protein, protein ligand, protein drug. Docking molecular an overview sciencedirect topics. The docking process is fast and consumes about 1020 min for a docking run. This yielded a total of 23 test cases supplementary table s2. This protein structure and a database of potential ligands serve as inputs to a docking program. Fiberdock flexible backbone and sidechain refinement and re. Although much improvement has been made in the field of protein protein docking, in the case of protein dna complexes, however, progress lags behind. The paradock algorithm contains four main stages illustrated in figure 2. 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. 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. 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.
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. Docking rigid, symmetric, protein protein, protein drug, protein dna, protein peptide patchdock rigid unbound docking of molecules. Which software should be used to do dnaprotein docking. Protein dna docking benchmark you can put your protein dna docking algorithm to the test using our protein dna benchmark. For protein dna docking, we assessed the use of a combined meta potential k. Computational methods such as docking have been developed to complement existing biophysical and structural biology techniques.
Which software should be used to do dna protein docking. 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. In this context, our pydock docking scheme, which has been successfully applied to model a significant number of protein. Molecular docking is also referred to as small molecular docking. It combines 1 gramm for global macromolecular docking, 2 scoring with a statistical potential, 3 clustering of bestscored structures, and 4 local refinement. Hex understands protein and dna structures in pdb format, and it can also read smallmolecule sdf files. Given the 3d structures of two molecules, determine the best binding modes. Proteinprotein and proteinligand docking intechopen. Predictive docking of proteinprotein and proteindna.
Mainly because the ligand docking code tends to assume that whats being docked is a single residue. Hex is an interactive protein docking and molecular superposition program, written by dave ritchie. Small molecule docking of dna repair proteins associated. The pathogenicity of the bacteria is enhanced by its developed dna repair mechanism. Protein docking is used to check the structure, position and orientation of a protein when it interacts with small molecules like ligands.
I know important residues of the protein, involved in interaction but which part of dna is important is. Proteinassisted rna fragment docking rnax for modeling. For the second method, we used a dna protein rigid docking method to compare the dna binding pattern of. 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. Protein receptorligand motifs fit together tightly, and are often referred to as a lock and key mechanism.
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. The results of two blind trials of protein docking are encouraging for complexes that are. Hydrogen donoracceptor complementarity protein drug. Moreover, hdock also supports proteinrnadna docking with an intrinsic. The dataset for protein dna docking was taken from the protein dna docking benchmark created by the bonvin group. 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. Molecular docking studies this chapter discusses about the molecular docking studies of the.
To perform a docking screen, the first requirement is a structure of the protein of interest. Attendees will be introduced to molecular docking technology and will have an opportunity to. Strategies for protein protein docking evaluation of the results of docking simulations. These configurations are evaluated using scoring functions to distinguish. Geometric docking algorithms based on the assumption of shape complementarity between the participating molecules. Results indicate hundreds of druglike and leadlike ligands. Docking and scoring incorporating a model of hydrophobic enclosure for protein. 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. Similarly, we have selected those cases with singlechain proteins and weakly homologous templates. 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. Pdf interfacial water molecules play an important role in many aspects of proteindna specificity and recognition. The benchmark contains 47 unboundunbound test cases of a varying degree of difficulty. Performance of the npdock server for protein dna complexes. Home software benchmark performance decoys zlab docking sites references.
Proteinrna and proteindna interactions play fundamental roles in. Pdf we present a proteindna docking benchmark containing 47 unbound unbound test cases of which are classified as easy, 22 as intermediate and 12. Protein rna and protein dna interactions play fundamental roles in many biological processes. The protein dna benchmark biomolecular docking aims at predicting the structure of a complex given the three dimensional structures of its components. Mode of interaction of the complexes with dna protein has also been supported by molecular docking. A detailed understanding of these interactions requires knowledge about protein nucleic acid complex structures. If youre lucky, its written generally enough such that it will dock a dna chain as well as a protein one. Dnaprotein binding, molecular docking, and in vitro. Protein rna interactions play an important role in many biological processes. To automatically make use of the binding information from the pdb in docking, here we have presented hdock, a novel web server of our hybrid docking algorithm. Computational prediction of protein rna complex structures includes two steps. Determining the complex structures of these interactions is valuable, in which molecular docking has played an important role. 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. The variety in test cases make this nonredundant benchmark a useful tool for comparison and further development of protein dna docking.
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. The cs ligand binds to seven amino acids of e protein by ten hydrogen bonds see table 3. This method has already been successful for designing dna protein and protein protein interfaces. Proteinrna docking using icm journal of chemical theory.
Profacgen employs computational docking techniques to search all possible binding modes in the translational and rotational space between the protein and nucleic acids dna, rna, or hybrid dna rna, which can undergo very large conformational changes upon complex formation. 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. Npdock nucleic acid protein dock is a web server for modeling of rna protein and dna protein complex structures. Symmdock prediction of complexes with c n symmetry. Predictive docking of protein protein and protein dna complexes. We present a new coarsegrained force field suitable for proteindna docking. The hdock server for integrated proteinprotein docking nature. Several methods for proteinprotein docking have been developed and. Further details can be found in the supplementary results. Protein protein and protein dna rna docking based on a hybrid algorithm of templatebased modeling and ab initio free docking. In order to avoid securityrelated warning messages when switching to secured connection, you may want either to. The antiproliferative activity, morphological changes, and apoptosis have been evaluated by mtt assay, acridine orangeethidium bromide aoetbr fluorescence staining, and dna ladder assay. How to study proteinligand interaction through molecular.
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. Thirumal kumar, in advances in protein chemistry and structural biology, 2014. Swissdock, a free protein ligand docking web service powered by eadock dss by the molecular modeling group of the swiss institute of bioinformatics. Bujnicki, details to be published elsewhere that comprises quasidnp, the dfire potential and a potential developed by varani et al. In this case, the bound structure is used for unbound docking. Proteindna docking with a coarsegrained force field bmc.
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. Protein protein and protein dna rna interactions play a fundamental role in a variety of biological processes. A better bet would likely be the protein protein docking code. Proteinprotein and protein ligand docking bioinfo3d.
Pdf homology modeling, molecular docking and dna binding. Macromolecular docking is the computational modelling of the quaternary structure of complexes formed by two or more interacting biological macromolecules. Firedock refinement and rescoring of rigidbody protein protein docking solutions. The docking protein is then phosphorylated on multiple tyrosine residues, leading to the recruitment of speci.
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