In silico study of the human rhodopsin and meta rhodopsin II/S-arrestin complexes: Impact of single point mutations related to retina degenerative diseases

Cupin superfamily proteins (TM1459) work as a macromolecular ligand framework with a double-stranded beta-barrel structure ligating to a Cu ion through histidine side chains. Variegating the first coordination sphere of TM1459 revealed that H52A and H54A/H58A mutants effectively catalyzed the diastereo- and enantio-selective Michael addition reaction of nitroalkanes to an α,β-unsaturated ketone. Moreover, in silico substrate docking signified C106N and F104W single-point mutations, which inverted the diastereoselectivity of H52A and further improved the stereoselectivity of H54A/H58A, respectively.

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Investigating the interaction between Organic Anion Transporter 1 and Ochratoxin A: an in silico structural study to depict early molecular events of substrate recruitment and the impact of single point mutations

Toxicology Letters ◽

10.1016/j.toxlet.2021.11.001 ◽

2021 ◽

Author(s):

Jochem Louisse ◽

Jean Lou C.M Dorne ◽

Luca Dellafiora

Keyword(s):

Ochratoxin A ◽

In Silico ◽

Organic Anion ◽

Single Point ◽

Point Mutations ◽

Organic Anion Transporter ◽

Anion Transporter ◽

Molecular Events ◽

Single Point Mutations ◽

The Impact

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Cupin Variants as Macromolecular Ligand Library for Stereoselective Michael Addition of Nitroalkanes

10.26434/chemrxiv.11481834 ◽

2019 ◽

Author(s):

Nobutaka Fujieda ◽

Haruna Ichihashi ◽

Miho Yuasa ◽

Yosuke Nishikawa ◽

Genji Kurisu ◽

...

Keyword(s):

Michael Addition ◽

In Silico ◽

Addition Reaction ◽

Single Point ◽

Point Mutations ◽

Unsaturated Ketone ◽

Michael Addition Reaction ◽

Beta Barrel ◽

Cupin Superfamily ◽

Single Point Mutations

Cupin superfamily proteins (TM1459) work as a macromolecular ligand framework with a double-stranded beta-barrel structure ligating to a Cu ion through histidine side chains. Variegating the first coordination sphere of TM1459 revealed that H52A and H54A/H58A mutants effectively catalyzed the diastereo- and enantio-selective Michael addition reaction of nitroalkanes to an α,β-unsaturated ketone. Moreover, in silico substrate docking signified C106N and F104W single-point mutations, which inverted the diastereoselectivity of H52A and further improved the stereoselectivity of H54A/H58A, respectively.

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Single point mutations can potentially enhance infectivity of SARS-CoV-2 revealed by in silico affinity maturation and SPR assay

10.1101/2020.12.24.424245 ◽

2020 ◽

Author(s):

Ting Xue ◽

Weikun Wu ◽

Ning Guo ◽

Chengyong Wu ◽

Jian Huang ◽

...

Keyword(s):

Binding Affinity ◽

In Silico ◽

Cell Attachment ◽

Single Point ◽

Point Mutations ◽

Cell Receptor ◽

Affinity Maturation ◽

Promising Target ◽

Assay Result ◽

Single Point Mutations

AbstractThe RBD (receptor binding domain) of the SARS-CoV-2 virus S (spike) protein mediates the viral cell attachment and serves as a promising target for therapeutics development. Mutations on the S-RBD may alter its affinity to cell receptor and affect the potency of vaccines and antibodies. Here we used an in-silico approach to predict how mutations on RBD affect its binding affinity to hACE2 (human angiotensin-converting enzyme2). The effect of all single point mutations on the interface was predicted. SPR assay result shows that 6 out of 9 selected mutations can strengthen binding affinity. Our prediction has reasonable agreement with the previous deep mutational scan results and recently reported mutants. Our work demonstrated in silico method as a powerful tool to forecast more powerful virus mutants, which will significantly benefit for the development of broadly neutralizing vaccine and antibody.

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In‐Silico Screening and Microsecond Molecular Dynamics Simulations to Identify Single Point Mutations That Destabilize β‐hexosaminidase A ( HexA ) Causing Tay‐Sachs Disease

Proteins Structure Function and Bioinformatics ◽

10.1002/prot.26180 ◽

2021 ◽

Author(s):

Ahmad Almanasra ◽

Brandon Havranek ◽

Shahidul M. Islam

Keyword(s):

Molecular Dynamics ◽

Molecular Dynamics Simulations ◽

In Silico ◽

Single Point ◽

Point Mutations ◽

In Silico Screening ◽

Tay Sachs Disease ◽

Hexosaminidase A ◽

Single Point Mutations ◽

Dynamics Simulations

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Single-Point Mutations in Qβ Virus-like Particles Change Binding to Cells

Biomacromolecules ◽

10.1021/acs.biomac.1c00443 ◽

2021 ◽

Author(s):

Marisa L. Martino ◽

Stephen N. Crooke ◽

Marianne Manchester ◽

M.G. Finn

Keyword(s):

Single Point ◽

Point Mutations ◽

Virus Like Particles ◽

Single Point Mutations

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MinD directly interacting with FtsZ at the H10 helix suggests a model for robust activation of MinC to destabilize FtsZ polymers

Biochemical Journal ◽

10.1042/bcj20170357 ◽

2017 ◽

Vol 474 (18) ◽

pp. 3189-3205 ◽

Cited By ~ 6

Author(s):

Ashoka Chary Taviti ◽

Tushar Kant Beuria

Keyword(s):

Cell Division ◽

Single Point ◽

Point Mutations ◽

Direct Interaction ◽

Ring Formation ◽

Z Ring ◽

Single Point Mutations ◽

Biochemical Analyses ◽

Ftsz Assembly ◽

The Mind

Cell division in bacteria is a highly controlled and regulated process. FtsZ, a bacterial cytoskeletal protein, forms a ring-like structure known as the Z-ring and recruits more than a dozen other cell division proteins. The Min system oscillates between the poles and inhibits the Z-ring formation at the poles by perturbing FtsZ assembly. This leads to an increase in the FtsZ concentration at the mid-cell and helps in Z-ring positioning. MinC, the effector protein, interferes with Z-ring formation through two different mechanisms mediated by its two domains with the help of MinD. However, the mechanism by which MinD triggers MinC activity is not yet known. We showed that MinD directly interacts with FtsZ with an affinity stronger than the reported MinC–FtsZ interaction. We determined the MinD-binding site of FtsZ using computational, mutational and biochemical analyses. Our study showed that MinD binds to the H10 helix of FtsZ. Single-point mutations at the charged residues in the H10 helix resulted in a decrease in the FtsZ affinity towards MinD. Based on our findings, we propose a novel model for MinCD–FtsZ interaction, where MinD through its direct interaction with FtsZ would trigger MinC activity to inhibit FtsZ functions.

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