PAbFold: Linear Antibody Epitope Prediction using AlphaFold2

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: April 19, 2024

Defining the binding epitopes of antibodies is essential for understanding how they bind to their antigens and perform molecular functions. However, while determining linear monoclonal can be accomplished utilizing well-established empirical procedures, these approaches are generally labor- time-intensive costly. To take advantage recent advances in protein structure prediction algorithms available scientific community, we developed a calculation pipeline based on localColabFold implementation AlphaFold2 that predict antibody by predicting complex between heavy light chains target peptide sequences derived from antigens. We found this pipeline, which call PAbFold, was able accurately flag known epitope several well-known targets (HA / Myc) when sequence broken into small overlapping peptides complementarity regions (CDRs) were grafted onto different framework single-chain fragment (scFv) format. determine if identify novel with no structural information publicly available, determined anti-SARS-CoV-2 nucleocapsid targeted using our method then experimentally validated computational results competition ELISA assays. These indicate AlphaFold2-based PAbFold capable identifying short time just sequences. This emergent capability sensitive methodological details such as length, neural network versions, multiple-sequence alignment database. at https://github.com/jbderoo/PAbFold.

Language: Английский

Modified heated CGMD simulations for discovering stable docked conformations of BiTE antibody against CD3 and CD117/c-kit

Molecular Simulation, Journal Year: 2024, Volume and Issue: 50(14), P. 1019 - 1038

Published: July 24, 2024

In cancer immunotherapy, the design and optimisation of bispecific antibodies hold great promise. Bispecific T-cell engager (BiTE) targeting CD3 CD117/c-kit have shown significant potential in experimental settings. Nevertheless, knowledge on their stable docked conformations at molecular level is still limited. This study presents an approach employing modified heated coarse-grained dynamics (CGMD) simulations to elucidate BiTE against CD117/c-kit. We integrated simulation with temperature control explore conformational landscape these complex interactions. The CGMD aimed re-assess poses suggested by ClusPro webserver. Furthermore, all-atomic trajectories unveiled dynamic residues formed throughout process. per-residue-energy-binding emphasised crucial amino acids involved binding within especially between complementarity-determining regions (CDR) BiTEs located N-terminal C-terminal CD3. formation three types interactions, such as hydrogen bonds, salt-bridge contact hydrophobic interactions plays a role motion, configuration free energy complexes. method valuable tool for rational drug field immunotherapy.

Language: Английский

Computational and in vitro analyses of the antibacterial effect of the ethanolic extract of Pluchea indica L. leaves

Biomedical Reports, Journal Year: 2024, Volume and Issue: 21(4)

Published: July 29, 2024

The most common gram-negative, Escherichia coli, and gram-positive bacteria, Bacillus spp., have evolved different mechanisms that caused the emergence of multi-drug resistance. As a result, drugs block bacterial growth cycle are needed. Here, in silico vitro studies were performed to assess compounds in Pluchea indica leaf extract, medicinal plant, can inhibit proteins. Briefly, P. leaves extracted using ethanol. crude extract was then subjected gas chromatography-mass spectrometry for metabolite screening. Molecular docking simulations with rhomboid protease (R^pro) (Protein data bank ID number: 3ZMI from E. coli filamenting temperature-sensitive mutant Z (FtsZ) protein 2VAM Bacillus subtilis performed. Moreover, well diffusion method used confirm antibacterial activity extract. A total 10 identified computational analysis. Based on drug-likeness prediction, may be drug-like molecules. Binding affinity tests indicated 10,10-Dimethyl-2,6-dimethylenebicyclo(7.2.0)undecan-5.β.-ol 11,11-Dimethyl-4,8-dimethylenebicyclo(7.2.0)undecan-3-ol had negative values. Accordingly, these potential ligands bind root mean square fluctuation values <2 Å, indicating stable binding ligand-protein complex. According assays, high concentration (50%) markedly inhibited B. subtilis, inhibitory zone diameters 31.86±1.63 21.09±0.09 mm, respectively. Overall, as functional inhibitors proteins via This facilitate development agents.

Language: Английский

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AlphaFold2 in biomedical research: facilitating the development of diagnostic strategies for disease

Hong Zhang,

Jiajing Lan,

Huijie Wang

et al.

Frontiers in Molecular Biosciences, Journal Year: 2024, Volume and Issue: 11

Published: July 30, 2024

Proteins, as the primary executors of physiological activity, serve a key factor in disease diagnosis and treatment. Research into their structures, functions, interactions is essential to better understand mechanisms potential therapies. DeepMind's AlphaFold2, deep-learning protein structure prediction model, has proven be remarkably accurate, it widely employed various aspects diagnostic research, such study biomarkers, microorganism pathogenicity, antigen-antibody missense mutations. Thus, AlphaFold2 serves an exceptional tool bridge fundamental research with breakthroughs diagnosis, developments strategies, design novel therapeutic approaches enhancements precision medicine. This review outlines architecture, highlights, limitations placing particular emphasis on its applications within grounded disciplines immunology, biochemistry, molecular biology, microbiology.

Language: Английский

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