
@article {123071,
	title = {Potential Self-Peptide Inhibitors of the SARS-CoV-2 Main Protease.},
	journal = {J Phys Chem B},
	year = {2023},
	month = {2023 Jan 23},
	abstract = {<p>The SARS-CoV-2 main protease (M) plays an essential role in viral replication, cleaving viral polyproteins into functional proteins. This makes M an important drug target. M consists of an N-terminal catalytic domain and a C-terminal α-helical domain (MC). Previous studies have shown that peptides derived from a given protein sequence (self-peptides) can affect the folding and, in turn, the function of that protein. Since the SARS-CoV-1 MC is known to stabilize its M and regulate its function, we hypothesized that SARS-CoV-2 MC-derived self-peptides may modulate the folding and the function of SARS-CoV-2 M. To test this, we studied the folding of MC in the presence of various self-peptides using coarse-grained structure-based models and molecular dynamics simulations. In these simulations of MC and one self-peptide, we found that two self-peptides, the α1-helix and the loop between α4 and α5 (loop4), could replace the equivalent native sequences in the MC structure. Replacement of either sequence in full-length M should, in principle, be able to perturb M function albeit through different mechanisms. Some general principles for the rational design of self-peptide inhibitors emerge: The simulations show that prefolded self-peptides are more likely to replace native sequences than those which do not possess structure. Additionally, the α1-helix self-peptide is kinetically stable and once inserted rarely exchanges with the native α1-helix, while the loop4 self-peptide is easily replaced by the native loop4, making it less useful for modulating function. In summary, a prefolded α1-derived peptide should be able to inhibit SARS-CoV-2 M function.</p>
},
	issn = {1520-5207},
	doi = {10.1021/acs.jpcb.2c05917},
	author = {Banerjee, Arkadeep and Gosavi, Shachi}
}
@article {102046,
	title = {Rational Design of Protein-Specific Folding Modifiers.},
	journal = {J Am Chem Soc},
	year = {2021},
	month = {2021 Nov 01},
	abstract = {<p>Protein-folding can go wrong and , with significant consequences for the living organism and the pharmaceutical industry, respectively. Here we propose a design principle for small-peptide-based protein-specific folding modifiers. The principle is based on constructing a "xenonucleus", which is a prefolded peptide that mimics the folding nucleus of a protein. Using stopped-flow kinetics, NMR spectroscopy, F{\"o}rster resonance energy transfer, single-molecule force measurements, and molecular dynamics simulations, we demonstrate that a xenonucleus can make the refolding of ubiquitin faster by 33 {\textpm} 5\%, while variants of the same peptide have little or no effect. Our approach provides a novel method for constructing specific, genetically encodable folding catalysts for suitable proteins that have a well-defined contiguous folding nucleus.</p>
},
	issn = {1520-5126},
	doi = {10.1021/jacs.1c09611},
	author = {Das, Anirban and Yadav, Anju and Gupta, Mona and R, Purushotham and Terse, Vishram L and Vishvakarma, Vicky and Singh, Sameer and Nandi, Tathagata and Banerjee, Arkadeep and Mandal, Kalyaneswar and Gosavi, Shachi and Das, Ranabir and Ainavarapu, Sri Rama Koti and Maiti, Sudipta}
}
