Hydrogen Bond Dynamic Propensity Studies for Protein Binding and Drug Design

Menéndez, Cintia A.; Accordino, Sebastián R.; Gerbino, Darío C.; Appignanesi, Gustavo A.

doi:10.1371/journal.pone.0165767

Cited by 44 publications

(19 citation statements)

References 24 publications

(54 reference statements)

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“…Hydrogen bonds are important contributors for the structure and interaction of protein-protein or ligand-receptor. In the drug design, hydrogen bond is critical to obtain the specificity of the drug to protein target [33][34][35]. In this study, malvidin-3-O-glucoside-caspase-3 interaction showed the number of hydrogen and hydrophobic bond lower than other anthocyanins, but performed the highest binding affinity.…”

Section: Resultsmentioning

confidence: 83%

Anti-Apoptotic Activity of Anthocyanins has Potential to inhibit Caspase-3 Signaling

Sari

Safitri

Cairns

et al. 2020

J.Trop.Life.Science

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Caspase-3 is a biochemical marker for cell apoptosis. Several studies focused on exploring caspase inhibitor potential in natural compounds. Hence, in this study, we investigated the anthocyanins as anti-apoptotic potential activity through caspase-3 using molecular docking. Six types of anthocyanin were retrieved from PubChem database and caspase-3 protein was downloaded from Protein Data Bank. Anthocyanins and caspase-3 protein were docked using HEX 8.0 program and visualized using Discovery Studio 4.1 software. The interaction among cyanidin-3-O-glucoside, delphinidin-3-O-glucoside, pelargonidin-3-O-glucoside, peonidin-3-O-glucoside and petunidin-3-O-glucoside showed similar binding pattern on caspase-3 protein. All of them bind to BIR2 region and allosteric site of caspase-3, which are a crucial site for apoptosis regulation. Interestingly, cyanidin-3-O-glucoside, delphinidin-3-O-glucoside, pelargonidin-3-O-glucoside and peonidin-3-O-glucoside are tightly bind to BIR2 region and allosteric sites with hydrogen bond and hydrophobic interaction. Even though malvidin-3-O-glucoside also interacted with caspase-3 in BIR1, BIR2 and BIR3 regions. This study implies that cyanidin-3-Oglucoside, delphinidin-3-O-glucoside, pelargonidin-3-O-glucoside and peonidin-3-O-glucoside are more potent as anti-apoptosis through binding to caspase-3 than other anthocyanins. Although all anthocyanins have potential as an inhibitor of caspase-3 protein and might have potential as anti-apoptosis. Further in-vitro and in-vivo studies are needed to confirm this experiment.

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Section: Resultsmentioning

confidence: 83%

Anti-Apoptotic Activity of Anthocyanins has Potential to inhibit Caspase-3 Signaling

Sari

Safitri

Cairns

et al. 2020

J.Trop.Life.Science

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“…Higher HB counts associated with the 33 -bound complexes could deduce an increase in the stability of the proteins [ 43 , 44 ]. Relatively, reduced average HBs (PknA = 122, PknB = 123) in the unbound proteins could possibly indicate an increase in structural flexibility or instability [ 43 , 45 ].…”

Section: Resultsmentioning

confidence: 99%

Probing the Highly Disparate Dual Inhibitory Mechanisms of Novel Quinazoline Derivatives against Mycobacterium tuberculosis Protein Kinases A and B

Olotu

2020

Molecules

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Mycobacterium tuberculosis (Mtb) serine/threonine (Ser/Thr) Protein kinases A (PknA) and B (PknB) have been identified as highly attractive targets for overcoming drug resistant tuberculosis. A recent lead series optimization study yielded compound 33 which exhibited potencies ~1000 times higher than compound 57. This huge discrepancy left us curious to investigate the mechanistic ‘dual’ (in)activities of the compound using computational methods, as carried out in this study. Findings revealed that 33 stabilized the PknA and B conformations and reduced their structural activities relative to 57. Optimal stability of 33 in the hydrophobic pockets further induced systemic alterations at the P-loops, catalytic loops, helix Cs and DFG motifs of PknA and B. Comparatively, 57 was more surface-bound with highly unstable motions. Furthermore, 33 demonstrated similar binding patterns in PknA and B, involving conserved residues of their binding pockets. Both π and hydrogen interactions played crucial roles in the binding of 33, which altogether culminated in high ΔGs for both proteins. On the contrary, the binding of 57 was characterized by unfavorable interactions with possible repulsive effects on its optimal dual binding to both proteins, as evidenced by the relatively lowered ΔGs. These findings would significantly contribute to the rational structure-based design of novel and highly selective dual inhibitors of Mtb PknA and B.

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“…It has been widely documented that the secondary structure of the protein can be stabilized by H-bonding. H-bonds between a protein and its ligand provide binding affinity and specificity of interaction [ 63 ]. A moderate mean number of H-bonds was exhibited between BEA and 3CLpro-pocket A (1–2), 3CLpro-pocket B (1–3), and S protein (0–4) as shown in Fig.…”

Section: Discussionmentioning

confidence: 99%