Biomolecular Solvation in Theory and Experiment

Feig, Michael

doi:10.1002/9783527629251.ch1

Cited by 4 publications

(8 citation statements)

References 202 publications

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“…It is also worth noting that the computational cost of most PB and GB methods scales extremely poorly with the system size and is comparable to explicit water simulations for large, globular molecules. 38 For this reason, several approximations and variations to the original GB approach have been introduced in order to improve the computational efficiency and the accuracy of the method. Many popular implicit solvent models such as the analytical continuum electrostatic method (ACE), 39 the fast analytical continuum treatment of solvation (FACTS) 40 as well as the accurate GBSW model 41 all belong to this category.…”

Section: Introductionmentioning

confidence: 99%

Variational Optimization of an All-Atom Implicit Solvent Force Field To Match Explicit Solvent Simulation Data

Bottaro

Lindorff‐Larsen

Best

2013

J. Chem. Theory Comput.

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The development of accurate implicit solvation models with low computational cost is essential for addressing many large-scale biophysical problems. Here, we present an efficient solvation term based on a Gaussian solvent-exclusion model (EEF1) for simulations of proteins in aqueous environment, with the primary aim of having a good overlap with explicit solvent simulations, particularly for unfolded and disordered states – as would be needed for multiscale applications. In order to achieve this, we have used a recently proposed coarse-graining procedure based on minimization of an entropy-related objective function to train the model to reproduce the equilibrium distribution obtained from explicit water simulations. Via this methodology, we have optimized both a charge screening parameter and a backbone torsion term against explicit solvent simulations of an α-helical and a β-stranded peptide. The performance of the resulting effective energy function, termed EEF1-SB, is tested with respect to the properties of folded proteins, the folding of small peptides or fast-folding proteins, and NMR data for intrinsically disordered proteins. The results show that EEF1-SB provides a reasonable description of a wide range of systems, but its key advantage over other methods tested is that it captures very well the structure and dimension of disordered or weakly structured peptides. EEF1-SB is thus a computationally inexpensive (~ 10 times faster than Generalized-Born methods) and transferable approximation for treating solvent effects.

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Section: Introductionmentioning

confidence: 99%

Variational Optimization of an All-Atom Implicit Solvent Force Field To Match Explicit Solvent Simulation Data

Bottaro

Lindorff‐Larsen

Best

2013

J. Chem. Theory Comput.

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“…It can act as a hydrogen-bond acceptor as well as a donor, allowing formation of a variety of structures that can easily adjust to changes in conditions. 6 In aqueous media, a well-defined number of H 2 O molecules directly surround the metal ion and are bound in the inner (or first) coordination sphere of the M III ion to form the hydrated [M(OH 2 ) n ] 3+ aqua complex, where n is the hydration (or coordination) number. A second shell of less ordered H 2 O molecules surrounds the first hydration sphere, forming a second (or outer) hydration sphere.…”

Section: Introductionmentioning

confidence: 99%

Improved Efficacy of Synthesizing *M^III-Labeled DOTA Complexes in Binary Mixtures of Water and Organic Solvents. A Combined Radio- and Physicochemical Study

et al. 2018

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Typically, the synthesis of radiometal-based radiopharmaceuticals is performed in buffered aqueous solutions. We found that the presence of organic solvents like ethanol increased the radiolabeling yields of [Ga]Ga-DOTA (DOTA = 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacatic acid). In the present study, the effect of organic cosolvents [ethanol (EtOH), isopropyl alcohol, and acetonitrile] on the radiolabeling yields of the macrocyclic chelator DOTA with several trivalent radiometals (gallium-68, scandium-44, and lutetium-177) was systematically investigated. Various binary water (HO)/organic solvent mixtures allowed the radiolabeling of DOTA at a significantly lower temperature than 95 °C, which is relevant for the labeling of sensitive biological molecules. Simultaneously, much lower amounts of the chelators were required. This strategy may have a fundamental impact on the formulation of trivalent radiometal-based radiopharmaceuticals. The equilibrium properties and formation kinetics of [M(DOTA)] (M= Ga, Ce, Eu, Y, and Lu) complexes were investigated in HO/EtOH mixtures (up to 70 vol % EtOH). The protonation constants of DOTA were determined by pH potentiometry in HO/EtOH mixtures (0-70 vol % EtOH, 0.15 M NaCl, 25 °C). The log K and log K values associated with protonation of the ring N atoms decreased with an increase of the EtOH content. The formation rates of [M(DOTA)] complexes increase with an increase of the pH and [EtOH]. Complexation occurs through rapid formation of the diprotonated [M(HDOTA)] intermediates, which are in equilibrium with the kinetically active monoprotonated [M(HDOTA)] intermediates. The rate-controlling step is deprotonation (and rearrangement) of the monoprotonated intermediate, which occurs through HO ( k) and OH ( k) assisted reaction pathways. The rate constants are essentially independent of the EtOH concentration, but the k values increase from Ce to Lu. However, the log K protonation constants, analogous to the log K value, decrease with increasing [EtOH], which increases the concentration of the monoprotonated M(HDOTA) intermediate and accelerates formation of the final complexes. The overall rates of complex formation calculated by the obtained rate constants at different EtOH concentrations show a trend similar to that of the complexation rates determined with the use of radioactive isotopes.

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“…Alternatively, continuum electrostatic models for the solvent [69, 63], which model it using a high dielectric continuum medium, are attracting attention. Their advantage is that they can greatly reduce the number of degrees of freedom of the simulated biological system; see Figure 1.1 for the surfaces of a biomolecule.…”

Section: Introductionmentioning

confidence: 99%

Fast Analytical Methods for Macroscopic Electrostatic Models in Biomolecular Simulations

Xu¹,

Cai²

2011

SIAM Rev.

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We review recent developments of fast analytical methods for macroscopic electrostatic calculations in biological applications, including the Poisson–Boltzmann (PB) and the generalized Born models for electrostatic solvation energy. The focus is on analytical approaches for hybrid solvation models, especially the image charge method for a spherical cavity, and also the generalized Born theory as an approximation to the PB model. This review places much emphasis on the mathematical details behind these methods.

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Biomolecular Solvation in Theory and Experiment

Cited by 4 publications

References 202 publications

Variational Optimization of an All-Atom Implicit Solvent Force Field To Match Explicit Solvent Simulation Data

Variational Optimization of an All-Atom Implicit Solvent Force Field To Match Explicit Solvent Simulation Data

Improved Efficacy of Synthesizing *M^III-Labeled DOTA Complexes in Binary Mixtures of Water and Organic Solvents. A Combined Radio- and Physicochemical Study

Fast Analytical Methods for Macroscopic Electrostatic Models in Biomolecular Simulations

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Biomolecular Solvation in Theory and Experiment

Cited by 4 publications

References 202 publications

Variational Optimization of an All-Atom Implicit Solvent Force Field To Match Explicit Solvent Simulation Data

Variational Optimization of an All-Atom Implicit Solvent Force Field To Match Explicit Solvent Simulation Data

Improved Efficacy of Synthesizing *MIII-Labeled DOTA Complexes in Binary Mixtures of Water and Organic Solvents. A Combined Radio- and Physicochemical Study

Fast Analytical Methods for Macroscopic Electrostatic Models in Biomolecular Simulations

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Improved Efficacy of Synthesizing *M^III-Labeled DOTA Complexes in Binary Mixtures of Water and Organic Solvents. A Combined Radio- and Physicochemical Study