Polarizable force fields for molecular dynamics simulations of biomolecules

Baker, Christopher M.

doi:10.1002/wcms.1215

Cited by 149 publications

(170 citation statements)

References 104 publications

(119 reference statements)

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“…Different polarizable force fields have been developed so far (AMBER ff02.pol, Drude, AMOEBA, etc.) . The AMOEBA polarizable force field may be more promising for high valent metal‐bearing solutions due to the inclusion of multipole electrostatics .…”

Section: Resultsmentioning

confidence: 99%

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Complexation Enhancement Drives Water‐to‐Oil Ion Transport: A Simulation Study

Qiao

Ferru

Ellis

2016

Chemistry A European J

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We address the structures and energetics of ion solvation in aqueous and organic solutions to understand liquid-liquid ion transport. Atomistic molecular dynamics (MD) simulations with polarizable force field are performed to study the coordination transformations driving lanthanide (Ln ) and nitrate ion transport between aqueous and an alkylamide-oil solution. An enhancement of the coordination behavior in the organic phase is achieved in contrast with the aqueous solution. In particular, the coordination number of Ce increases from 8.9 in the aqueous to 9.9 in the organic solutions (from 8 in the aqueous to 8.8 in the organic systems for Yb ). Moreover, the local coordination environment changes dramatically. Potential of mean force calculations show that the Ln -ligand coordination interaction strengths follow the order of Ln -nitrate>Ln -water>Ln -DMDBTDMA. They increase 2-fold in the lipophilic environment in comparison to the aqueous phase, and we attribute this to the shedding of the outer solvation shell. Our findings highlight the importance of outer sphere interactions on the competitive solvation energetics that cause ions to migrate between immiscible phases; an essential ingredient for advancing important applications such as rare earth metal separations. Some open questions in simulating the coordination behavior of heavy metals are also addressed.

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Section: Resultsmentioning

confidence: 99%

“…. The AMOEBA polarizable force field may be more promising for high valent metal‐bearing solutions due to the inclusion of multipole electrostatics . Very recently, Marjolin et al., reported the AMOEBA force field parameters for some Ln III (La 3+ , Eu 3+ , Gd 3+ ) and actinide(III) (Ac 3+ , Am 3+ , Cm 3+ ) ions.…”

Section: Resultsmentioning

confidence: 99%

Complexation Enhancement Drives Water‐to‐Oil Ion Transport: A Simulation Study

Qiao

Ferru

Ellis

2016

Chemistry A European J

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“…However, while local diffusion of the water and ethanol components of the solvent near a peptide hydrogen are slowed a factor of 2 to 3 relative to diffusion in the bulk solvent, calculations done with Equation indicate that, at the RF used for our experiments (500 MHz), calculated

σ_{ETH}^{NOE}

are relatively insensitive to diffusion and that a 3‐fold change in bulk diffusion coefficient could not produce the overestimates of

σ_{ETH}^{NOE}

that are obtained from calculations with the MD trajectories. Some consideration beyond local solvent molecule diffusion seems to be required. Better agreement between observed and calculated properties of ethanol‐water solutions can be obtained by using more elaborate force fields in simulations, particularly those that include the effects of electronic polarizability . Adjustment of the parameters for the water component of these solutions may also enhance agreement …”

Section: Discussionmentioning

confidence: 99%

Examination of ethanol interactions with Trp‐cage peptide through MD simulations and intermolecular nuclear Overhauser effects

Gerig

2018

J of Physical Organic Chem

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Molecular dynamic (MD) simulations of the model protein Trp‐cage dissolved in 35% ethanol‐water at 298 K have been carried out using conventional force fields. The goal was to develop a better understanding of experimental intermolecular nuclear Overhauser effects (NOEs) that arise from interactions of ethanol methyl groups with hydrogens of the peptide. Cross‐relaxation terms ( σETHNOE) for peptide N‐H hydrogens and several side chain groups were calculated from the MD trajectories. The simulations indicate that water preferentially solvates hydrogens at the peptide termini while ethanol preferentially accumulates at the other hydrogens of the peptide. Most of a calculated NOE arises from interaction of ethanol molecules in the first solvent layer with a peptide hydrogen. Calculated σETHNOE are qualitatively consistent with experimental values but are not in quantitative agreement. Results from MD trajectories calculated by using modified force fields for ethanol intended to reduce peptide‐methyl group interactions do not lead to better agreement between observed and calculated σETHNOE. Possible reasons for the poor predictions of σETHNOE from the MD trajectories are discussed.

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“…The AMBER force field has been shown to accurately reproduce the structural and dynamic properties of a large variety of canonical and noncanonical nucleic acids in water . To improve the description of electrostatic interactions, polarizable force fields have also been developed to include a change in the charge distribution in a molecule in response to its environment . The CHARMM polarizable force field for nucleic acids is based on a classical Drude oscillator model and was developed and validated on unsubstituted and alkyl‐substituted adenine, guanine, cytosine, uracil, and thymine bases, hydrated crystals, and hydrogen bonded base pairs.…”

Section: Existing Methodology For Predicting Small Molecule—rna Intermentioning

confidence: 99%

Modeling of ribonucleic acid–ligand interactions

Stefaniak

Chudyk

Bodkin

et al. 2015

WIREs Comput Mol Sci

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Computational methods play a pivotal role in the early stages of small molecule drug discovery and are widely applied in virtual screening, structure optimization, and compound activity profiling. Over the past half century in medicinal chemistry, almost all the attention has been directed to protein-ligand binding and computational tools were created with such targets in mind. However, with growing discoveries of functional RNAs and their possible applications, RNA macromolecules have gained considerable attention as possible drug targets. This flow of discovery was followed by adapting existing computational tools for RNA applications as well as active development of new RNA-tailored methods. However, due to the different nature of RNA, especially its tendency to use morphological plasticity (conformational change in ligand binding) this remains a challenging task. The evolution of 'protein-based' drug discovery and related computational methods offers some clues on possible future directions and developments in modeling RNA interactions with small molecule ligands. The function of many RNAs is modulated by small ligand molecules. These can be naturally occurring molecules as well as fully synthetic compounds. One of the most-studied and well-validated targets for small molecules is ribosomal RNA (rRNA), which forms the active site of the ribosome. This large macromolecular complex consists of RNA and proteins, and is responsible for protein synthesis. Blockage of ribosome function disrupts protein synthesis and leads to cell death. That is why the bacterial ribosome is a good target for many groups of small molecule antibiotics, including macrolides, aminoglycosides, tetracyclines, or oxazolidines, among others.2 Riboswitches represent another class of RNA molecules that can be modulated upon small molecule binding. They typically occur within the protein-noncoding parts of messenger RNA (mRNA) and regulate the translation of the protein-coding parts. Riboswitches can directly form complexes with small molecules and, in this way, regulate gene function without the presence of protein cofactors. Among natural ligands recognized by riboswitches are metabolites, divalent cations, and second messengers. [3][4][5] As riboswitches are common in bacteria and rarely occur in eukaryotes, they are emerging as a potential target for new and selective antibacterial drugs. Viral RNAs can also be † The authors wish it to be known that F.S. and E.I.C. contributed equally and should be regarded as Joint First Authors. 425targets for small molecule inhibitors. Examples include HIV-1 trans-activation response (TAR) RNA, for which small molecules 6-8 and peptidomimetics 9,10 that disrupt its interactions with the Tat protein have been described. Among other druggable viral RNAs are the Hepatitis C virus (HCV) internal ribosome entry site [11][12][13] and the Hepatitis D virus (HDV) ribozyme.14 In recent years, considerable attention has centered on micro RNA (miRNA) as a possible drug target in many diseases including inflamma...

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Polarizable force fields for molecular dynamics simulations of biomolecules

Cited by 149 publications

References 104 publications

Complexation Enhancement Drives Water‐to‐Oil Ion Transport: A Simulation Study

Complexation Enhancement Drives Water‐to‐Oil Ion Transport: A Simulation Study

Examination of ethanol interactions with Trp‐cage peptide through MD simulations and intermolecular nuclear Overhauser effects

Modeling of ribonucleic acid–ligand interactions

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