Insights on the binding mechanisms and structural dynamics of protamine-DNA interaction.

It has been more than a century since the protamines were found. Protamine continues to exist as a nucleo-protamine complex, similar to how the histone does. In sperm cells of vertebrates, protamine binds to DNA to produce compact chromatin.

AT vs GC binding of protamine-template: A microscopic understanding through molecular dynamics and binding free energies.

Protamine, an arginine-rich protein, compacts DNA more tightly than histones in somatic cells, yet its sequence-specific binding remains unclear. Using all-atom MD simulations with an arginine-rich short cationic peptide that mimics the protamine characteristics, we discovered distinct sequence preferences: the peptide binds preferentially to GC-rich sequences in the major groove and AT-rich sequences in the minor groove. Our structural analysis reveals that GC-rich binding induces significant DNA bending, narrowing the major groove and enhancing peptide interactions.

DNA compaction and chromatin dynamics: The role of cationic polyamines and proteins.

DNA compaction by polyaminic cations and proteins involves reversible condensation mechanisms. Polyamines, metal cations, and histone proteins are utilized to compact lengthy DNA chains. Chromatin organization begins with nucleosomal arrays, further compacted by linker histones.

A review on salt-induced DNA compaction and charge inversion.

This review delves into the reversible process of DNA compaction, vital for cellular functions like replication and transcription. The study highlights how various cations assist in the condensation of DNA chains, highlighting their specificity. The impact of the ionic environment on chromatin characteristics is discussed, emphasizing the roles of mono- and divalent cations in neutralizing DNA charge and promoting compaction.

DNA groove preference shift upon phosphorylation of a protamine-like cationic peptide.

Protamines, arginine-rich DNA-binding proteins, are responsible for chromatin compaction in sperm cells, but their DNA groove preference, major or minor, is not clearly identified. We herein study the DNA groove preference of a short protamine-like cationic peptide before and after phosphorylation, using all-atom molecular dynamics and umbrella sampling simulations. According to various thermodynamic and structural analyses, a peptide in its non-phosphorylated native state prefers the minor groove over the major groove, but phosphorylation of the peptide bound to the minor groove not only reduces its binding affinity but also brings a serious deformation of the minor groove, eliminating the minor-groove preference.

Effect of phosphorylation of protamine-like cationic peptide on the binding affinity to DNA.

Protamines are more arginine-rich and more basic than histones and are responsible for providing a highly compacted shape to the sperm heads in the testis. Phosphorylation and dephosphorylation are two events that occur in the late phase of spermatogenesis before the maturation of sperms. In this work, we have studied the effect of phosphorylation of protamine-like cationic peptides using all-atom molecular dynamics simulations.

Diameter Dependent Melting and Softening of dsDNA Under Cylindrical Confinement.

Carbon nanotubes (CNTs) are considered promising candidates for biomolecular confinement, including DNA encapsulation for gene delivery. Threshold values of diameters have been reported for double-stranded DNA (dsDNA) encapsulation inside CNTs. We have performed all-atom molecular dynamics (MD) simulations of dsDNAs confined inside single-walled CNTs (SWCNTs) at the physiologically relevant temperature of 300 K.

Nanoscale structures and mechanics of peptide nucleic acids.

Peptide nucleic acids (PNAs) are charge-neutral polyamide oligomers having extremely favorable thermal stability and high affinity to cell membranes when coupled with cationic cell-penetrating peptides (CPPs), as well as the encouraging antisense and antigene activity in cell-free systems. The study of the mechanical properties of short PNA molecules is rare both in experiments and theoretical calculations. Here, we studied the microscopic structures and elastic properties; namely, persistence length, stretch modulus, twist-stretch coupling, and structural crookedness of double-stranded PNA (dsPNA) and their hybrid derivatives using all-atom MD simulation and compared them with those of double-stranded DNA (dsDNA) and double-stranded RNA (dsRNA).