The PDBbind Database:  Collection of Binding Affinities for Protein−Ligand Complexes with Known Three-Dimensional Structures

Wang, Renxiao; Fang, Xueliang; Lu, Yuele; Wang, Shaomeng

doi:10.1021/jm030580l

Cited by 866 publications

(909 citation statements)

References 26 publications

(37 reference statements)

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“…Second, inhibitors of PARP and PTP were taken from the results of a combination of both virtual and high-throughput screening [26,27]. Third, the PDBbind database [28] was used to generate a large number of additional cases for testing screening utility. From the full 800 complex set, all proteins were identified that were represented with at least five different ligands.…”

Section: Pham Screening Enrichment Setmentioning

confidence: 99%

Surflex-Dock 2.1: Robust performance from ligand energetic modeling, ring flexibility, and knowledge-based search

Jain

2007

J Comput Aided Mol Des

541

502

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The Surflex flexible molecular docking method has been generalized and extended in two primary areas related to the search component of docking. First, incorporation of a small-molecule force-field extends the search into Cartesian coordinates constrained by internal ligand energetics. Whereas previous versions searched only the alignment and acyclic torsional space of the ligand, the new approach supports dynamic ring flexibility and allatom optimization of docked ligand poses. Second, knowledge of well established molecular interactions between ligand fragments and a target protein can be directly exploited to guide the search process. This offers advantages in some cases over the search strategy where ligand alignment is guided solely by a ''protomol'' (a pre-computed molecular representation of an idealized ligand). Results are presented on both docking accuracy and screening utility using multiple publicly available benchmark data sets that place Surflex's performance in the context of other molecular docking methods. In terms of docking accuracy, Surflex-Dock 2.1 performs as well as the best available methods. In the area of screening utility, Surflex's performance is extremely robust, and it is clearly superior to other methods within the set of cases for which comparative data are available, with roughly double the screening enrichment performance.

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Section: Pham Screening Enrichment Setmentioning

confidence: 99%

Surflex-Dock 2.1: Robust performance from ligand energetic modeling, ring flexibility, and knowledge-based search

Jain

2007

J Comput Aided Mol Des

541

502

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“…The majority of cellular adhesion molecules bind with energies near 10kT, making the individual bonds reversible. [65][66][67] Also worth mentioning is the importance of the binding kinetics. Binding and unbinding rate constants comprise a "state space" in which different families of adhesion molecules reside and accomplish their function.…”

Section: Introductionmentioning

confidence: 99%

Beyond Molecular Recognition: Using a Repulsive Field to Tune Interfacial Valency and Binding Specificity between Adhesive Surfaces

et al. 2008

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Surface-bound biomolecular fragments enable "smart" materials to recognize cells and other particles in applications ranging from tissue engineering and medical diagnostics to colloidal and nanoparticle assembly. Such smart surfaces are, however, limited in their design to biomolecular selectivity. This feature article demonstrates, using a completely nonbiological model system, how specificity can be achieved for particle (and cell) binding, employing surface designs where immobilized nanoscale adhesion elements are entirely nonselective. Fundamental principles are illustrated by a model experimental system where 11 nm cationic nanoparticles on a planar negative silica surface interact with flowing negative silica microspheres having 1.0 and 0.5 µm diameters. In these systems, the interfacial valency, defined as the number of cross-bonds needed to capture flowing particles, is tunable through ionic strength, which alters the range of the background repulsion and therefore the effective binding strength of the adhesive elements themselves. At high ionic strengths where long-range electrostatic repulsions are screened, single surface-bound nanoparticles capture microspheres, defining the univalent regime. At low ionic strengths, competing repulsions weaken the effective nanoparticle adhesion so that multiple nanoparticles are needed for microparticle capture. This article discusses important features of the univalent regime and then illustrates how multivalency produces interfacial-scale selectivity. The arguments are then generalized, providing a possible explanation for highly specific cell binding in nature, despite the degeneracy of adhesion molecules and cell types. The mechanism for the valency-related selectivity is further developed in the context of selective flocculation in the colloidal literature. Finally, results for multivalent binding are contrasted with the current thinking for interfacial design and the presentation of adhesion moieties on engineered surfaces.

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“…Since the QSAR score was originally trained by kinaseinhibitor dissociation constant, an indirect indicator of kinase (Liu et al, 2007) and PDBbind (Wang et al, 2004) databases.…”

Section: Virtual Screening Of Rho Inhibitor Candidatesmentioning

confidence: 99%

Stepwise high-throughput virtual screening of Rho kinase inhibitors from natural product library and potential therapeutics for pulmonary hypertension

Yan

et al. 2015

Pharmaceutical Biology

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(2015) Stepwise high-throughput virtual screening of Rho kinase inhibitors from natural product library and potential therapeutics for pulmonary hypertension, Pharmaceutical Biology, 53:8, 1201-1206, DOI: 10.3109/13880209.2014 ORIGINAL ARTICLEStepwise high-throughput virtual screening of Rho kinase inhibitors from natural product library and potential therapeutics for pulmonary hypertension Hao Su, Ji Yan, Jian Xu, Xi-Zhen Fan, Xian-Lin Sun, and Kang-Yu Chen Department of Cardiology, Anhui Provincial Hospital, Hefei, China Abstract Context: Pulmonary hypertension (PH) is a devastating disease characterized by progressive elevation of pulmonary arterial pressure and vascular resistance due to pulmonary vasoconstriction and vessel remodeling. The activation of RhoA/Rho-kinase (ROCK) pathway plays a central role in the pathologic progression of PH and thus the Rho kinase, an essential effector of the ROCK pathway, is considered as a potential therapeutic target to attenuate PH. Objective: In the current study, a synthetic pipeline is used to discover new potent Rho inhibitors from various natural products. Materials and methods: In the pipeline, the stepwise high-throughput virtual screening, quantitative structure-activity relationship (QSAR)-based rescoring, and kinase assay were integrated. The screening was performed against a structurally diverse, drug-like natural product library, from which six identified compounds were tested to determine their inhibitory potencies agonist Rho by using a standard kinase assay protocol. Results: With this scheme, we successfully identified two potent Rho inhibitors, namely phloretin and baicalein, with activity values of IC 50 ¼ 0.22 and 0.95 mM, respectively. Discussion and conclusion: Structural examination suggested that complicated networks of nonbonded interactions such as hydrogen bonding, hydrophobic forces, and van der Waals contacts across the complex interfaces of Rho kinase are formed with the screened compounds.

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The PDBbind Database: Collection of Binding Affinities for Protein−Ligand Complexes with Known Three-Dimensional Structures

Cited by 866 publications

References 26 publications

Surflex-Dock 2.1: Robust performance from ligand energetic modeling, ring flexibility, and knowledge-based search

Surflex-Dock 2.1: Robust performance from ligand energetic modeling, ring flexibility, and knowledge-based search

Beyond Molecular Recognition: Using a Repulsive Field to Tune Interfacial Valency and Binding Specificity between Adhesive Surfaces

Stepwise high-throughput virtual screening of Rho kinase inhibitors from natural product library and potential therapeutics for pulmonary hypertension

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