Soumen Barman

Soumen Barman

Publications

You can also find my articles on my Google Scholar profile.

Amyloid β‑Peptide Segment Conjugated Side-Chain Proline-Based Polymersas Potent Inhibitors in Lysozyme Amyloidosis

Published in Bioconjugate Chem., 2024

This study introduces a novel approach to inhibit amyloidosis using peptides derived from the amyloid-promoting sequence of amyloid β-peptide, conjugated with side-chain proline-based methacrylate polymers. These conjugates effectively inhibit lysozyme amyloidosis and reduce cytotoxicity of amyloid aggregations. Synthesized di-, tri-, and tetra-peptide conjugated chain transfer agents (CTAs) were used to polymerize Boc-proline methacryloyloxyethyl ester, resulting in water-soluble polymers with defined peptide chain ends. Among these, the LVFF-conjugated polymer demonstrated potent inhibition of lysozyme amyloidosis, supported by spectroscopic, microscopic, and computational analyses. This study highlights the potential of combining segment-derived amyloid β-peptide sequences with side-chain proline-based polymers for targeting amyloidosis.

Recommended citation: Nayak K, Ghosh P, Barman S, Sudhamalla B, Theato P, De P. Amyloid β-Peptide Segment Conjugated SideChain Proline-Based Polymers as Potent Inhibitors in Lysozyme Amyloidosis. Bioconjugate Chemistry. 2024 Feb 12. https://pubs.acs.org/doi/10.1021/acs.bioconjchem.3c00509

Uncovering the non-histone interactome of the BRPF1 bromodomain using site-specific azide-acetyllysine photochemistry

Published in JBC, 2023

BRPF1, a member of the bromodomain-containing protein family, recognizes acetylated histones and non-histone transcription factors to regulate gene expression. While its role in histone recognition is well understood, its regulation via non-histone acetylation remains unexplored. We utilized a protein engineering approach to identify non-histone interactors of BRPF1. By introducing a photo-cross-linkable amino acid into its bromodomain, we efficiently cross-linked interacting partners, revealing novel associations through proteomics. One such partner, interleukin enhancer–binding factor 3, was validated and investigated for its role in hepatocellular carcinoma using ChIP-seq and RNA-seq datasets. These findings enhance our understanding of BRPF1’s transcriptional regulation and aid in developing cancer therapeutics.

Recommended citation: Barman S , Padhan J, Sudhamalla B. Uncovering the Nonhistone Interactome of BRPF1 Bromodomain Using SiteSpecific Azide-Acetyllysine Photochemistry. JBC. 2023 Dec 3; DOI:https://doi.org/10.1016/j.jbc.2023.105551. https://www.sciencedirect.com/science/article/pii/S0021925823025796?via%3Dihub

Integrated virtual screening and MD simulation approaches toward discovering potential inhibitors for targeting BRPF1 bromodomain in hepatocellular carcinoma

Published in Journal of Molecular Graphics and Modelling, 2023

Hepatocellular carcinoma (HCC) is a deadly cancer with limited treatment options. We analyzed bromodomain-containing proteins (BRPF) in HCC and found BRPF1 to be significantly upregulated, correlating with poor patient survival. Targeting BRPF1 could improve HCC treatment. We employed high-throughput virtual screening and machine learning-based QSAR modeling to identify new BRPF1 inhibitors. Through extensive molecular dynamics simulations, we discovered four lead compounds with promising binding affinity for the BRPF1 bromodomain, suggesting their potential as potent inhibitors for HCC therapy.

Recommended citation: Barman S, Bardhan I, Padhan J, Sudhamalla B.Integrated virtual screening and MD simulation approaches toward discovering potential inhibitors for targeting BRPF1 bromodomain in hepatocellular carcinoma. Journal of Molecular Graphics and Modelling. 2023, 108642, ISSN 1093-3263. https://www.sciencedirect.com/science/article/pii/S1093326323002401?via%3Dihub

Novel insights into the recognition of acetylated histone H4 tail by the TRIM24 PHD-Bromo module

Published in Biochem J., 2023

TRIM24 is a chromatin reader that activates estrogen-dependent genes in tumor development. It ubiquitinates p53 and binds a specific histone signature (H3K4me0/H3K23ac) via its RING, PHD, and Bromo domains. High TRIM24 and H3K23ac levels predict poor breast cancer survival. We explored TRIM24 binding to acetylated histone H4 (H4ac). TRIM24 PHD-Bromo preferentially binds H4K5ac, H4K8ac, and H4K5acK8ac. This binding doesn’t interfere with PHD’s recognition of H3K4me0. H4K5ac and H4K8ac co-localize near gene transcription start sites in breast cancer. TRIM24-H4ac targets are linked to vital biological pathways, suggesting a role in transcriptional regulation.

Recommended citation: Bardhan I, Barman S, Roy A, Sudhamalla B. Novel insights into the recognition of acetylated histone H4 tail by the TRIM24 PHD-Bromo module. Biochem J. 2023 May 17; 480 (9): 629-647. https://portlandpress.com/biochemj/article-abstract/480/9/629/232921/Novel-insights-into-the-recognition-of-acetylated?redirectedFrom=fulltext

Insulin fibril inhibition using glycopolymeric nanoassemblies

Published in Biomater Sci., 2023

We synthesized block copolymers via RAFT polymerization, containing Boc-protected leucine and Ac-protected glucose. Deprotection yielded amphiphilic polymers forming nano aggregates in water inhibited insulin fibrillation through hydrophobic, electrostatic, and hydrogen bonding interactions. Biophysical techniques confirmed the inhibition, with molecular dynamics simulations supporting the findings.

Recommended citation: Bera A, Ghosh P, Barman S, Bhattacharya S, Sudhamalla B, Goswami K, De P. Insulin fibril inhibition using glycopolymeric nanoassemblies. Biomater Sci. 2023 Mar 31:1-13. https://pubs.rsc.org/en/content/articlelanding/2023/bm/d2bm02078e

Uncovering the Domain-Specific Interactome of the TAF1 Tandem Reader Using Site-Specific Azide-Acetyllysine Photochemistry

Published in Biochemistry, 2023

In this study, we investigated how TAF1 dual bromodomain mediates crosstalk among histone modifications. We engineered TAF1 to carry a photoactivatable amino acid, AzF and created analogs targeting each bromodomain separately and both together. Structural integrity was confirmed, and binding properties to acetylated histone ligands were characterized. Both bromodomains independently recognized unique interacting partners at the cellular level. Our findings suggest that BD1 and BD2 of the TAF1 tandem reader independently regulate downstream cellular functions by recognizing specific interacting partners.

Recommended citation: Yadav Y, Barman S#, Roy A#, Padhan J, Sudhamalla B. Uncovering the Domain-Specific Interactome of the TAF1 Tandem Reader Using Site-Specific Azide-Acetyllysine Photochemistry. Biochemistry. 2023 Jan 17;62(2):270-280 https://pubs.acs.org/doi/10.1021/acs.biochem.2c00140

Identification of novel natural product inhibitors of BRD4 using high throughput virtual screening and MD simulation

Published in J Biomol Struct Dyn, 2022

Bromodomains, vital in gene expression regulation, are implicated in various diseases, making them targets for therapeutic intervention. BRD4, a well-studied bromodomain in cancers like AML and Burkitt Lymphoma, has attracted attention for inhibitor development. However, existing inhibitors often lack specificity and safety. Our study screened natural compounds from the NPASS database against BRD4-BD1 using computational methods. Five inhibitors with comparable or superior binding affinity compared to JQ1 were identified, including NPC268484 (Palodesangren-B), NPC295021 (Candidine), and NPC313112 (Buxifoliadine-D). These findings offer potential candidates for further validation in future experimental studies.

Recommended citation: Barman S, Sahoo SS, Padhan J, Sudhamalla B. Identification of novel natural product inhibitors of BRD4 using high throughput virtual screening and MD simulation. J Biomol Struct Dyn. 2022 Dec 16:1-13. https://www.tandfonline.com/doi/abs/10.1080/07391102.2022.2155346

Molecular Insights into the Recognition of Acetylated Histone Modifications by the BRPF2 Bromodomain.

Published in Biochemistry, 2022

BRPF2, a crucial partner of HBO1 histone acetyltransferase complex, plays a role in directing the complex to chromatin for gene expression regulation. Our study unveils BRPF2’s bromodomain as capable of recognizing various acetyllysine residues on histones H4, H3, and H2A, with a preference for H4K5ac, H4K8ac, and H4K5acK12ac modifications. Mutational analysis of the bromodomain identifies key residues for acetyllysine binding. Additionally, ChIP-seq analysis shows BRPF2 co-localizes with HBO1 at H4K5ac and H4K8ac marks near transcription start sites, highlighting its role in chromatin recruitment for gene regulation.

Recommended citation: Barman S, Roy A, Padhan J, Sudhamalla B. Molecular Insights into the Recognition of Acetylated Histone Modifications by the BRPF2 Bromodomain. Biochemistry. 2022 Sep 6;61(17):1774-1789. https://pubs.acs.org/doi/10.1021/acs.biochem.2c00297

Insights into the Molecular Mechanisms of Histone Code Recognition by the BRPF3 Bromodomain

Published in Chem Asian J., 2021

BRPF3 is a crucial scaffold protein in gene transcription regulation, forming a complex with HBO1 histone acetyltransferase. Our study reveals that BRPF3 bromodomain interacts with mono- and di-acetylated histone peptides (H4K5ac and H4K5acK12ac). Pull-down assays with full-length histones confirm this interaction. Molecular dynamics simulations illustrate the binding mechanism and stability of the bromodomain-histone peptide complexes. These findings shed light on how BRPF3 directs HBO1 complex recruitment to chromatin for transcriptional regulation.

Recommended citation: Barman S, Roy A, Bardhan I, Kandasamy T, Shivani S, Sudhamalla B. Insights into the Molecular Mechanisms of Histone Code Recognition by the BRPF3 Bromodomain. Chem Asian J. 2021 Nov 2;16(21):3404-3412. https://onlinelibrary.wiley.com/doi/10.1002/asia.202100793

Engineering an acetyllysine reader with a photocrosslinking amino acid for interactome profiling

Published in Chem Commun (Camb), 2021

The site-specific installation of light-activable crosslinker unnatural amino acids offers a powerful approach to trap transient protein–protein interactions both in vitro and in vivo. Herein, we engineer a bromodomain to introduce 4-benzoyl-L-phenylalanine (BzF) using amber suppressor mutagenesis without compromising its ability to recognize the acetylated histone proteins. We demonstrate the high crosslinking efficiency of the engineered reader towards the interacting partners and its suitability for profiling the transient bromodomain interactome.

Recommended citation: Roy A, Barman S, Padhan J, Sudhamalla B. Engineering an acetyllysine reader with a photocrosslinking amino acid for interactome profiling. Chem Commun (Camb). 2021 Sep 28;57(77):9866-9869 https://pubs.rsc.org/en/content/articlelanding/2021/cc/d1cc04611j