FireDock: a web server for fast interaction refinement in molecular docking

Mashiach, Efrat; Stroopinsky, Dina; Andrusier, Nelly; Nussinov, Ruth; Wolfson, Haim J.

doi:10.1093/nar/gkn186

Cited by 679 publications

(499 citation statements)

References 39 publications

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“…Using the crystal structure of [KS3][AT3] 12 and NMR structure of the ACP2 domain, 11 computational docking simulations guided by the experimental constraints were performed (see Experimental Procedures for details). 14,15 The resulting model (Fig. 5) accounts for the biophysical data presented here and is also in agreement with the previously published biochemical findings.…”

Section: Protein-protein Interactions Between Holo-acp2 and Ks3 Of Debssupporting

confidence: 89%

“…As a first step toward understanding the proteinprotein and enzyme-substrate interactions involved in the translocation of a polyketide from ACP2 to KS3, we transferred backbone amide 1 H and 15 N assignments obtained previously at pH 5.5 11 to the more physiological pH of 7. This reassignment was necessary because the 190-kDa homodimeric [KS3][AT3] didomain protein was inactive under the more acidic conditions.…”

Section: Assignment Of Acp2 At a Physiological Phmentioning

confidence: 99%

“…This reassignment was necessary because the 190-kDa homodimeric [KS3][AT3] didomain protein was inactive under the more acidic conditions. By titrating apo-ACP2 in sodium phosphate buffer from pH 5.5 to 7.0, the amide resonances in 2D [ 1 H, 15 N]-HSQC spectra could be followed to the latter pH value (Fig. 3).…”

Section: Assignment Of Acp2 At a Physiological Phmentioning

confidence: 99%

“…Significantly, the location of the C-terminus of ACP2 in our model is consistent with the proposed model for the interaction between the Cterminus docking domain attached to the ACP and the N-terminal coiled coil domain present on the KS partner. 16 To ascertain whether or not the observed changes in the [ 1 H, 15 (Fig. 6).…”

Section: Protein-protein Interactions Between Holo-acp2 and Ks3 Of Debsmentioning

confidence: 99%

“…To visualize the complementary roles of enzymesubstrate and protein-protein interactions during intermodular chain translocation, we sought to develop stable models for this transient process that would be amenable to analysis by [ 1 H, 15 N]-HSQC spectroscopy. It is known that the KS active site harbors the binding pocket for the incoming polyketide chain during this interthiol transfer reaction.…”

Section: Synthesis Of Cf 3 -S-coamentioning

confidence: 99%

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Probing the interactions of an acyl carrier protein domain from the 6‐deoxyerythronolide B synthase

et al. 2011

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The assembly-line architecture of polyketide synthases (PKSs) provides an opportunity to rationally reprogram polyketide biosynthetic pathways to produce novel antibiotics. A fundamental challenge toward this goal is to identify the factors that control the unidirectional channeling of reactive biosynthetic intermediates through these enzymatic assembly lines. Within the catalytic cycle of every PKS module, the acyl carrier protein (ACP) first collaborates with the ketosynthase (KS) domain of the paired subunit in its own homodimeric module so as to elongate the growing polyketide chain and then with the KS domain of the next module to translocate the newly elongated polyketide chain. Using NMR spectroscopy, we investigated the features of a structurally characterized ACP domain of the 6-deoxyerythronolide B synthase that contribute to its association with its KS translocation partner. Not only were we able to visualize selective protein-protein interactions between the two partners, but also we detected a significant influence of the acyl chain substrate on this interaction. A novel reagent, CF 3 -S-ACP, was developed as a 19 F NMR spectroscopic probe of protein-protein interactions. The implications of our findings for understanding intermodular chain translocation are discussed.

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Section: Protein-protein Interactions Between Holo-acp2 and Ks3 Of Debssupporting

confidence: 89%

Section: Assignment Of Acp2 At a Physiological Phmentioning

confidence: 99%

Section: Assignment Of Acp2 At a Physiological Phmentioning

confidence: 99%

Section: Protein-protein Interactions Between Holo-acp2 and Ks3 Of Debsmentioning

confidence: 99%

Section: Synthesis Of Cf 3 -S-coamentioning

confidence: 99%

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Probing the interactions of an acyl carrier protein domain from the 6‐deoxyerythronolide B synthase

et al. 2011

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Docking, Scoring, and Virtual Screening in Drug Discovery

Spyrakis

Sarkar

Kellogg

2021

Burger's Medicinal Chemistry and Drug Discovery

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Since its introduction about four decades ago, docking and scoring are now the very heart of structure‐based drug design. The past 10–20 years have seen a plethora of docking and scoring tools successfully integrated into drug discovery pipelines. Interestingly, while artificial intelligence is now receiving significant attention in the computational modeling arena, docking and scoring have long utilized these techniques. This comprehensive summary highlights some of the most significant achievements of docking and scoring, reviews the current status, provides descriptions of many of the tools available, comments on some of the outstanding challenges facing the paradigm, and offers perspectives and advice on best practices for users. While significant development is still needed in docking of flexible molecules and accurate Gibb's free energy predictions, docking and scoring are very useful when handled by experienced practitioners, but less so if treated as a “black box.” Lastly, we present a hypothetical case so beginners may appreciate the nuances of setting up a docking study. Focus in docking is now shifting toward parallel applications, i.e. protein–protein, protein–oligosaccharide, protein–DNA, or protein–RNA docking and polypharmacology. In summary, this article is intended to elucidate the nuances of the subject, while providing guidelines for practical implementation of effective workflows in drug discovery and structural biology.

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Characterization of molecular interactions between Escherichia coli RNA polymerase and topoisomerase I by molecular simulations

et al. 2016

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Escherichia coli topoisomerase I (EctopoI), a type IA DNA topoisomerase, relaxes the negative DNA supercoiling generated by RNA polymerase (RNAP) during transcription elongation. Due to the lack of structural information on the complex, the exact nature of the RNAP-EctopoI interactions remains unresolved. Herein, we report for the first time, the structure-based modeling of the RNAP-EctopoI interactions using computational methods. Our results predict that the salt-bridge as well as hydrogen bond interactions are responsible for the formation and stabilization of the RNAP-EctopoI complex. Our investigations provide molecular insights for understanding how EctopoI interacts with RNAP, a critical step for preventing hypernegative DNA supercoiling during transcription.

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FireDock: a web server for fast interaction refinement in molecular docking

Cited by 679 publications

References 39 publications

Probing the interactions of an acyl carrier protein domain from the 6‐deoxyerythronolide B synthase

Probing the interactions of an acyl carrier protein domain from the 6‐deoxyerythronolide B synthase

Docking, Scoring, and Virtual Screening in Drug Discovery

Characterization of molecular interactions between Escherichia coli RNA polymerase and topoisomerase I by molecular simulations

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