共查询到20条相似文献,搜索用时 15 毫秒
1.
Background
A relevant problem in drug design is the comparison and recognition of protein binding sites. Binding sites recognition is generally based on geometry often combined with physico-chemical properties of the site since the conformation, size and chemical composition of the protein surface are all relevant for the interaction with a specific ligand. Several matching strategies have been designed for the recognition of protein-ligand binding sites and of protein-protein interfaces but the problem cannot be considered solved. 相似文献2.
Thomas G Kristensen Jesper Nielsen Christian NS Pedersen 《Algorithms for molecular biology : AMB》2010,5(1):9
Background
The fingerprint of a molecule is a bitstring based on its structure, constructed such that structurally similar molecules will have similar fingerprints. Molecular fingerprints can be used in an initial phase of drug development for identifying novel drug candidates by screening large databases for molecules with fingerprints similar to a query fingerprint. 相似文献3.
Yogendra Patel Catherine A Heyward Michael RH White Douglas B Kell 《BMC systems biology》2011,5(1):32
Background
The similarity property principle has been used extensively in drug discovery to identify small compounds that interact with specific drug targets. Here we show it can be applied to identify the interactions of small molecules within the NF-κB signalling pathway. 相似文献4.
5.
Alessandro Siglioccolo Alessandro Paiardini Maria Piscitelli Stefano Pascarella 《BMC structural biology》2011,11(1):1-12
Background
Disrupting protein-protein interactions by small organic molecules is nowadays a promising strategy employed to block protein targets involved in different pathologies. However, structural changes occurring at the binding interfaces make difficult drug discovery processes using structure-based drug design/virtual screening approaches. Here we focused on two homologous calcium binding proteins, calmodulin and human centrin 2, involved in different cellular functions via protein-protein interactions, and known to undergo important conformational changes upon ligand binding.Results
In order to find suitable protein conformations of calmodulin and centrin for further structure-based drug design/virtual screening, we performed in silico structural/energetic analysis and molecular docking of terphenyl (a mimicking alpha-helical molecule known to inhibit protein-protein interactions of calmodulin) into X-ray and NMR ensembles of calmodulin and centrin. We employed several scoring methods in order to find the best protein conformations. Our results show that docking on NMR structures of calmodulin and centrin can be very helpful to take into account conformational changes occurring at protein-protein interfaces.Conclusions
NMR structures of protein-protein complexes nowadays available could efficiently be exploited for further structure-based drug design/virtual screening processes employed to design small molecule inhibitors of protein-protein interactions. 相似文献6.
Background
Many molecules are flexible and undergo significant shape deformation as part of their function, and yet most existing molecular shape comparison (MSC) methods treat them as rigid bodies, which may lead to incorrect shape recognition. 相似文献7.
Markus Sällman Almén Karl JV Nordström Robert Fredriksson Helgi B Schiöth 《BMC biology》2009,7(1):50-14
Background
Membrane proteins form key nodes in mediating the cell's interaction with the surroundings, which is one of the main reasons why the majority of drug targets are membrane proteins. 相似文献8.
Background
Chemical bonding of the drug onto surfaces by means of spacer molecules is accompanied with a reduction of the biological activity of the drug due to a constricted mobility since normally only short spacer molecule like aminopropyltrimethoxysilane (APMS) are used for drug coupling. This work aimed to study covalent attachment of heparin to titanium(oxide) surfaces by varying the length of the silane coupling agent, which should affect the biological potency of the drug due to a higher mobility with longer spacer chains. 相似文献9.
Rudra P Saha Ranjit P Bahadur Arumay Pal Saptarshi Mandal Pinak Chakrabarti 《BMC structural biology》2006,6(1):11-5
Background
Molecular recognition is all pervasive in biology. Protein molecules are involved in enzyme regulation, immune response, signal transduction, oligomer assembly, etc. Delineation of physical and chemical features of the interface formed by protein-protein association would allow us to better understand protein interaction networks on one hand, and to design molecules that can engage a given interface and thereby control protein function on the other hand. 相似文献10.
Flavien Quintus Olivier Sperandio Julien Grynberg Michel Petitjean Pierre Tuffery 《BMC bioinformatics》2009,10(1):245
Background
Virtual screening methods are now well established as effective to identify hit and lead candidates and are fully integrated in most drug discovery programs. Ligand-based approaches make use of physico-chemical, structural and energetics properties of known active compounds to search large chemical libraries for related and novel chemotypes. While 2D-similarity search tools are known to be fast and efficient, the use of 3D-similarity search methods can be very valuable to many research projects as integration of "3D knowledge" can facilitate the identification of not only related molecules but also of chemicals possessing distant scaffolds as compared to the query and therefore be more inclined to scaffolds hopping. To date, very few methods performing this task are easily available to the scientific community. 相似文献11.
Background
A polypeptide chain of a protein-protein complex is said to be obligatory if it is bound to another chain throughout its functional lifetime. Such a chain might not adopt the native fold in the unbound form. A non-obligatory polypeptide chain associates with another chain and dissociates upon molecular stimulus. Although conformational changes at the interaction interface are expected, the overall 3-D structure of the non-obligatory chain is unaltered. The present study focuses on protein-protein complexes to understand further the differences between obligatory and non-obligatory interfaces. 相似文献12.
Jérémie Neasta Sandrine Uttenweiler-Joseph Karima Chaoui Bernard Monsarrat Jean-Claude Meunier Lionel Moulédous 《Proteome science》2006,4(1):23-10
Background
Opiate addiction reflects plastic changes that endurably alter synaptic transmission within relevant neuronal circuits. The biochemical mechanisms of these adaptations remain largely unknown and proteomics-based approaches could lead to a broad characterization of the molecular events underlying adaptations to chronic drug exposure. 相似文献13.
Background
Protein-protein interactions play essential roles in protein function determination and drug design. Numerous methods have been proposed to recognize their interaction sites, however, only a small proportion of protein complexes have been successfully resolved due to the high cost. Therefore, it is important to improve the performance for predicting protein interaction sites based on primary sequence alone. 相似文献14.
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16.
Background
Interaction of a drug or chemical with a biological system can result in a gene-expression profile or signature characteristic of the event. Using a suitably robust algorithm these signatures can potentially be used to connect molecules with similar pharmacological or toxicological properties by gene expression profile. Lamb et al first proposed the Connectivity Map [Lamb et al (2006), Science 313, 1929–1935] to make successful connections among small molecules, genes, and diseases using genomic signatures. 相似文献17.
Background
Several studies have suggested that proteins that interact with more partners evolve more slowly. The strength and validity of this association has been called into question. Here we investigate how biases in high-throughput protein–protein interaction studies could lead to a spurious correlation. 相似文献18.
19.
Background
The study and comparison of protein-protein interfaces is essential for the understanding of the mechanisms of interaction between proteins. While there are many methods for comparing protein structures and protein binding sites, so far no methods have been reported for comparing the geometry of non-covalent interactions occurring at protein-protein interfaces.Methodology/Principal Findings
Here we present a method for aligning non-covalent interactions between different protein-protein interfaces. The method aligns the vector representations of van der Waals interactions and hydrogen bonds based on their geometry. The method has been applied to a dataset which comprises a variety of protein-protein interfaces. The alignments are consistent to a large extent with the results obtained using two other complementary approaches. In addition, we apply the method to three examples of protein mimicry. The method successfully aligns respective interfaces and allows for recognizing conserved interface regions.Conclusions/Significance
The Galinter method has been validated in the comparison of interfaces in which homologous subunits are involved, including cases of mimicry. The method is also applicable to comparing interfaces involving non-peptidic compounds. Galinter assists users in identifying local interface regions with similar patterns of non-covalent interactions. This is particularly relevant to the investigation of the molecular basis of interaction mimicry. 相似文献20.
Thomas Kuhn Egon L Willighagen Achim Zielesny Christoph Steinbeck 《BMC bioinformatics》2010,11(1):159