Heterogeneous Dynamical Environment at the Interface of a Protein–DNA Complex

Abstract

Binding between protein and DNA is an essential process to regulate different biological activities. Two puzzling questions in protein−DNA recognition are (i) how the protein's binding domain identifies the DNA sequence in an aqueous solution and (ii) how the formation of the complex alters the dynamical environment around it. In this work, we present results obtained from molecular dynamics simulations of the N-terminal α-helical domain of the λ-repressor protein (in dimeric form) bound to the corresponding operator DNA. Effects of formation of the complex in modifying the microscopic dynamics of water as well as the kinetics of hydrogen bonds at the interface have been explored. Locally heterogeneous restricted water motions at the complex interface have been observed, the extent of restriction being more significant around the directly bound residues of the protein and the DNA. In particular, the calculation revealed the existence of significantly constrained motionally restricted water layer that can form either bridges around the directly bound residues of the protein and DNA or are engaged in forming water-mediated contacts between a fraction of the unbound residues. More importantly, it is observed that the restricted water motion around the complex is correlated with the hydrogen bond relaxation time scale at the interface. It is further demonstrated that the kinetics of water−water hydrogen bonds involving the bridged water are influenced more due to complex formation.

Vibrational spectrum and randomness of water at the interface of a protein–DNA complex

“…In this work, we attempt to explore it. As reported Springer Nature 2021 L A T E X template Vibrational Spectrum and Randomness of Water at the Interface of a Protein-DNA Comple earlier [23], the calculations are based on two separate types of water, (i) hydration layer water and (ii) bridged water. The former types are located within 5 Å from any residue (either bound or unbound) of protein or DNA.…”

“…Recently, we investigated in detail the microscopic properties of the hydrated λ-repressor protein-DNA complex [21][22][23]. It is showed that complex formation not only modifies the conformational behavior of the DNA and protein, but also it impacts the local arrangement of the surrounding water along with their motional activities.…”

“…On the other hand, the later types are always situated within 4 Å of both the DNA and the protein components. It may be noted that such water molecules exhibit highly restricted motions as they remain simultaneously bound to both the components by forming hydrogen-bonded bridges [23]. The bound residues of DNA or protein that are engaged in direct contact, are written in our earlier work [23].…”

“…The concurrent presence of ordered, doublycoordinated and triply-coordinated less ordered interfacial water molecules was revealed from the analysis. Attempts have also been made to examine how complex formation alters the dynamical environment of the hydration layer [23].…”

Conformational Properties of Aβ Peptide Oligomers in Aqueous Ionic Liquid Solution: Insights from Molecular Simulation Studies

“…30 In addition, site specific heterogeneous dynamics of water and IL components around the peptide monomers have also been studied. 31 In the present work, we have performed molecular dynamics (MD) simulations to probe the effects of binary aqueous solutions containing [BMIM][BF 4 ] as the IL on the conformational properties of Aβ 17−42 oligomers of different orders. Efforts have been made to gain microscopic insights into preferential distributions of the water and IL components at the interface and their influence on the structural distortions and stabilities of the oligomers.…”