Conformational fluctuations of a protein–DNA complex and the structure and ordering of water around it

Sinha, Sudipta Kumar; Bandyopadhyay, Sanjoy

doi:10.1063/1.3670877

Cited by 13 publications

(11 citation statements)

References 59 publications

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“…We note that the local tetrahedral metric is a very convenient metric for measuring the local structure of water at biomolecular as well as inorganic interfaces. [72][73][74][75][76][77][78][79][80][81] The tagged molecule potential energy (TPE or u tag ), defined as the interaction energy of an individual water molecule with all other molecules in the system, is a convenient measure of local energy. [82][83][84][85][86] The TPE can also be considered as the binding energy of an individual water molecule in the system.…”

Section: Characterizing Order and Energetics In The Hydration Layermentioning

confidence: 99%

Sensitivity of local hydration behaviour and conformational preferences of peptides to choice of water model

Nayar

Chakravarty

2014

Phys. Chem. Chem. Phys.

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Hydration of the 16-residue β-hairpin fragment of the protein in the folded and unfolded ensembles is studied with mTIP3P and TIP4P solvent models using the CHARMM22 protein force-field. mTIP3P is a three-site water model which is used for parameterization of the CHARMM force-field and is known to exhibit liquid-state anomalies of water at temperatures about 80 K lower than the experimental temperature. TIP4P is a four-site water model which gives a better description of the experimental phase diagram and liquid-state anomalies of water. At a temperature of 250 K, where the folded ensemble of the peptide is stable and the unfolded ensemble is metastable, secondary structure metrics are much more sensitive to the choice of solvent model in the unfolded, rather than folded, ensemble. In particular, mean values as well as variation in the positional root mean square displacements (RMSD) and configurational entropy are greater in mTIP3P compared to the TIP4P solvent. The peptide structure is relatively more compact in the TIP4P solvent, which supports unfolded as well as hydrophobic core states. In terms of average local order and binding energy of the water surrounding the peptide, strong deviations from bulk behaviour are restricted to the first hydration shell and differences between the folded and unfolded ensembles in the two solvents are small. The strong coupling between the solvent and the peptide is demonstrated, however, by the dependence of the unfolding temperature on the water model (400 K in mTIP3P and 465 K in TIP4P) and the qualitatively different temperature dependence of the hydration layer occupancy signalling the unfolding transition in the two solvents. A residue-wise decomposition of different contributions to the configurational energy indicates that the TIP4P solvent shows far greater variation in the interaction with charged sidegroups of amino acid residues than the mTIP3P solvent. The implications of sequence-dependent sensitivity of peptide secondary structures to the choice of water models for simulating folding-unfolding equilibria and free energy landscapes are discussed.

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Section: Characterizing Order and Energetics In The Hydration Layermentioning

confidence: 99%

Sensitivity of local hydration behaviour and conformational preferences of peptides to choice of water model

Nayar

Chakravarty

2014

Phys. Chem. Chem. Phys.

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“…Map describing the interactions between TRF1 and telomeric DNA as determined by solution NMR (Protein Data Bank entry 1IV6 16 ). Direct readout (red line), indirect readout (black dotted line), and hydrophobic patches (black broken line) are delineated.…”

Section: Figmentioning

confidence: 99%

A Comprehensive Model for the Recognition of Human Telomeres by TRF1

Garton

Laughton

2013

Journal of Molecular Biology

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Eukaryotic chromosomes are capped by telomeres, nucleoprotein complexes that prevent chromosome end-to-end fusions and control cell ageing. Two proteins in this complex, telomere repeat binding factors (TRF1 and TRF2), specifically recognise the double-stranded TTAGGG tandem repeat sequence. TRF1 is a homodimer with roles governing DNA architecture and negatively regulating telomere length. We explore the conformational space of this protein–DNA complex using molecular dynamics and, for the first time, generate a complete model of TRF1–DNA recognition that has not been possible on the basis of crystallographic and NMR data alone. The results reconcile previous conflicting experimental models for the sequence selectivity of the recognition process, by confirming many of the findings while identifying important new interactions and behaviour. This improved characterisation also reveals extensive indirect readout, which suggests that recognition will be affected by changes to DNA helical parameters such as bending.

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“…Molecular dynamics (MD) simulation provides an important alternative method that has been used over the years to explore the properties of hydrated protein–DNA complexes. − In particular, water-mediated interactions between the protein and the DNA molecules in complexed states have been studied. , Recently, Poon and co-workers discussed the role of water in protein–DNA recognition. They demonstrated that configurationally similar water-mediated contacts play a distinct role during the recognition process of the DNA by the transcription factors belonging to the ETS-Family.…”

Section: Introductionmentioning

confidence: 99%

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

Mondal

Bandyopadhyay

2020

Langmuir

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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.

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Conformational fluctuations of a protein–DNA complex and the structure and ordering of water around it

Cited by 13 publications

References 59 publications

Sensitivity of local hydration behaviour and conformational preferences of peptides to choice of water model

Sensitivity of local hydration behaviour and conformational preferences of peptides to choice of water model

A Comprehensive Model for the Recognition of Human Telomeres by TRF1

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

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