Molecular Simulation of Peptide Interactions with an RP-HPLC Sorbent

Yarovsky, Irene; Hearn, Milton Thomas William; Aguilar, Mibel

doi:10.1021/jp972232z

Cited by 44 publications

(30 citation statements)

References 44 publications

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“…The effect of the water environment can be seen in a comparison of ASA values of the same peptide measured in either solution or in vacuum ( Table 1, columns 4 and 5). The molecular conformation of the peptide tends to be more open in an aqueous environment, a finding in keeping with earlier results examining the conformation of peptides in water-organic solvent environments or when associated with immobilized non-polar n-alkyl chains [23,24] . Table 1.…”

Section: Resultssupporting

confidence: 87%

A study on the atomic hydrophobicity of peptides in aqueous solutions using molecular dynamics modeling methods

et al. 2008

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Accurate quantification of the hydrophobic/hydrophilic properties of protein surfaces requires detailed knowledge of the hydrophobicity of amino acids at the atomic level. As discussed previously in various published papers, molecular modeling can be used with effect to acquire such knowledge. In this study, molecular dynamics methods have been employed to examine the role of the distance between an amino acid atom and its nearest water molecule in relation to its intrinsic atom hydrophobicity. This distance is the radius of the water-excluding-region around the atom; therefore, it can provide information on the solvent accessibility and steric hindrance that may influence the atom hydrophobicity. Molecular models of tripeptide in the form of GXG, and pentapeptides in the form of AcWLXLL-NH 2 and AcGGXGG-NH 2 for 20 natural amino acids in the X position were constructed and allowed to dynamically interact with surrounding water for a sufficient period of time. The distance value for each atom in all natural amino acids were calculated and analyzed against the atom/amino acid's other parameters such as radial distribution function, solvent-accessible surface area, and hydrogen bonding. It was observed that, when the dynamic factor is taken into account, peptide molecular conformation is modified noticeably with residue type. For protein surface identification purposes, preliminary results are consistent with those reported in the literature on the need to include the amino acid structural properties as well as the effects of its neighboring residues. Further investigation is envisaged in order to verify these observations. BACKGROUNDIn peptides the hydrophobicity of amino acids plays an important role in their structural and dynamic properties as well as for their bioactivity in peptide-protein, or peptide-surface interactions. Knowledge of these properties is needed in studies of many biological processes, for biomedical applications, or in the design of nanostructures which aim to interact in a purposeful, predictive manner with peptides and proteins. Numerous hydrophobicity scales for amino acids and amino acid residues have been reported in the literature. Most of these scales are of low resolution and do not consider molecular dynamics and steric effects. However, such information is important for the prediction of the impact of drugs on protein surfaces.Computer-aided studies have been increasingly used to complement the experimental hydrophobicity data, which are often difficult to obtain due to the complex nature of peptides and their interactions with the surrounding environment. Using a least-squares fit approach for free energy of transfer from n-octanol to water against 5 amino acid atom types, namely C, N/O, N + , O -, and S, Eisenberg et al. [1,2] were able to construct a hydrophobicity scale for all 20 natural amino acids. The fit used the linear relationship between the free energy of transfer and the amino acid surface exposure to surrounding solvents for nonpolar amino acid groups [3] , which was...

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Section: Resultssupporting

confidence: 87%

A study on the atomic hydrophobicity of peptides in aqueous solutions using molecular dynamics modeling methods

et al. 2008

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“…[236] Other elegant procedures, such as the procedure developed by Hearn et al (see Figure 28) to identify chromatographic binding domains of proteins in RPC via proteolytic cleavage [237] or the use of probe molecules in carefully designed chromatographic experiments, [238] may also reveal valuable information regarding the three-dimensional structures of proteins, their orientation as well as the extent of unfolding upon binding. Owing to this complexity, the ability of the solvophobic theory to adequately describe and predict the molecular details of peptide and protein interactions in RPC is limited from a quantitative view point.…”

Section: Fundamentals Of Reversed Phase Chromatography 1047mentioning

confidence: 99%

Fundamentals of Reversed Phase Chromatography: Thermodynamic and Exothermodynamic Treatment

Vailaya

2005

Journal of Liquid Chromatography & Related Technologies

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Reversed phase chromatography (RPC) is the most popular branch of HPLC for the analysis and purification of a wide variety of substances. Despite significant advances in both our knowledge and understanding of the fundamental principles governing the retention behavior in RPC, there is considerable debate in the literature regarding the mechanism of retention. This review addresses the theoretical foundation of the chromatographic technique, with an emphasis on thermodynamic and exothermodynamic treatment of retention equilibrium, as well as their implication on the mechanistic aspects of RPC retention. A unified and rigorous treatment based on the solvophobic theory is reviewed in terms of its ability to shed light on the physicochemical underpinnings of the retention in RPC, and to quantitatively predict the retention behavior of nonpolar compounds, acids and bases, and peptides and proteins. Also highlighted are areas of future challenges in the theory and practice of RPC, potentially leading to a better quantitative understanding and use of the popular technique. It is undoubtedly the unsung champion of the modern biological sciences, enabling the intricacies of cellular biology to be at last discriminated in detail. [2] Without the recent advances in HPLC, modern biology, functional genomics, and proteomics would not exist. The incredible power of HPLC to discern the molecular diversity of biological phenomena is largely attributed to its ability to distinguish mass differences as little as 1 Da in a macromolecule, such as proteins when coupled with mass spectrometry, [3,4] to separate proteins that differ by only a single amino acid, [5] to separate conformational isomers of a long chain polypeptide, [6] and to resolve the different tertiary conformational structures of DNA fragments. [7] The exquisite sensitivity, the speed, and the impressive resolving power of modern HPLC find application in various fields, such as pharmaceutical, food and clinical analysis, pollution control, downstream processing, measurement of physicochemical properties of drugs as well as the separation of peptides, proteins, and nucleic acids. At the heart of the HPLC revolution is the mode of separation that we are all familiar with-reversed phase chromatography (RPC). The seminal works of Horváth and co-workers [8 -11] have contributed significantly to the theory and practice of RPC, resulting in its wide acceptance by the scientific community as a high resolution separation technique of choice. It is estimated that approximately 80% of HPLC analysis is conducted in this mode. [12] The success of this technique is attributed to the employment of microparticulate alkyl-silica monomeric bonded phases, such as octadecylated silica, which offers high separation efficiency combined with unparalleled convenience, versatility and reproducibility. The use of bonded hydrocarbonaceous stationary phases having a variety of functional groups and a wide choice of hydroorganic eluents to modulate retention offer a broad range of operating con...

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“…The solid surfaces modified with tethered chains have been extensively studied in recent years due to their importance for a wide range of technological processes, such as adhesion, colloidal stabilization, lubrication, drug delivery, nanotechnology and chromatography [1][2][3]. The theoretical studies included scaling theories [4,5], self-consistent field methods [6][7][8][9][10][11][12][13], single chain mean-field methods [14][15][16], density functional theories [17][18][19][20][21][22][23][24][25] and computer simulations [26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41]. The structure of the polymer layer can play a fundamental role in these processes.…”

Section: Introductionmentioning

confidence: 99%

A density functional study of the structure of tethered chains in a binary mixture

Borówko¹,

Staszewski²

2012

Condens. Matter Phys.

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A density functional study of the structure of a layer formed by chain molecules pinned to a solid surface is presented. The chains are modeled as freely joined spheres. Segments and all components interact via LennardJones (12-6) potential. The interactions of fluid molecules with the wall are described by the Lennard-Jones (9-3) potential. We analyze how different parameters of the model affect the dependence of the brush height upon the mixture composition. We consider the effect of grafting density and the parameters characterizing the interactions of fluid molecules with the substrate and with the chains as well as interactions within the mixture. The changes in the brush height correlate with the adsorption of particular components.

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Molecular Simulation of Peptide Interactions with an RP-HPLC Sorbent

Cited by 44 publications

References 44 publications

A study on the atomic hydrophobicity of peptides in aqueous solutions using molecular dynamics modeling methods

A study on the atomic hydrophobicity of peptides in aqueous solutions using molecular dynamics modeling methods

Fundamentals of Reversed Phase Chromatography: Thermodynamic and Exothermodynamic Treatment

A density functional study of the structure of tethered chains in a binary mixture

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