Peptide models. 1. Topology of selected peptide conformational potential energy surfaces (glycine and alanine derivatives)

Perczel, András; Ángyán, János G.; Kajtár, M.; Viviani, Wladia; Rivail, Jean‐Louis; Marcoccia, John Frank; Csizmadia, Imre G.

doi:10.1021/ja00016a049

Cited by 256 publications

(239 citation statements)

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“…42 The less optimal (Table 3) centered by Asn forms a strong backbone H-bond between the NH group of Gly and the carbonyl oxygen of cysteine in position 1 (1.86 Å), reducing the chance of Asn isomerization. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 In conclusion, based on its structural properties revealed by CD and NMR 2 could be highly resistant against succinimide ring formation and thus, against decomposition.…”

Section: Chemo-stability Of Cyclic Ngr-peptidesmentioning

confidence: 99%

Development of Cyclic NGR Peptides with Thioether Linkage: Structure and Dynamics Determining Deamidation and Bioactivity

Enyedi¹,

Czajlik

Knapp³

et al. 2015

J. Med. Chem.

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Abstract AbstractIn drug targeting NGR-peptides recognized by CD13 receptors on tumor neovasculature have got improved interest. Here we present the synthesis and structure analysis of novel thioether linked cyclic NGR-peptides. We found that chemo-stability (resistance against spontaneous decomposition forming isoAsp and Asp derivatives) strongly depends both on sample handling conditions and structural properties. Significant correlation was found between chemo-stability and structural measures: e.g. NH Gly …CO Asn-sc distances. Side chain orientation of Asn is the key determining factor, if turned away from HN Gly chemo-stability increases. Structure stabilizing factors (e.g. H-bond(s)) lower their internal dynamics and thus macromolecules become even more resistant against spontaneous decomposition. Effect of cyclic NGR-peptides on cell adhesion was examined on A2058 melanoma cell lines. It was found that some of them gradually increased the cell adhesion with long term characteristics indicating the time-dependent formation of integrin binding isoAsp derivatives, responsible for the adhesion inducing effect.

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Section: Chemo-stability Of Cyclic Ngr-peptidesmentioning

confidence: 99%

Development of Cyclic NGR Peptides with Thioether Linkage: Structure and Dynamics Determining Deamidation and Bioactivity

Enyedi¹,

Czajlik

Knapp³

et al. 2015

J. Med. Chem.

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“…(C) An alternative short-hand notation of the same minima seen in some other publications. 18 theory. All these computations were performed at all levels of theory without (case A) and with (case B) BSSE correction.…”

Section: Computational Detailsmentioning

confidence: 99%

Stability issues of covalently and noncovalently bonded peptide subunits

et al. 2004

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Abstract:The present study focuses on important questions associated with modeling of peptide and protein stability.Computing at different levels of theory (RHF, B3LYP) for a representative ensemble of conformers of di-and tripeptides of alanine, we found that the Gibbs Free Energy values correlate significantly with the total electronic energy of the molecules (0.922 Յ R 2 ). For noncovalently attached but interacting peptide subunits, such as [For-NH 2 ] 2 or [For-L-Ala-NH 2 ] 2 , we have found, as expected, that the basis set superimposition error (BSSE) is large in magnitude for small basis set but significantly smaller when larger basis sets [e.g., B3LYP/6-311ϩϩG(d,p)] are used. Stability of the two hydrogen bonds of antiparallel ␤-pleated sheets were quantitatively determined as a function of the molecular structure, S10 and S14, computed as 4.0 Ϯ 0.5 and 8.1 Ϯ 1.1 kcal/mol, respectively. Finally, a suitable thermoneutral isodesmic reaction was introduced to scale both covalently and noncovalently attached peptide units onto a common stability scale. We found that a suitable isodesmic reaction can result in the total electronic energy as well as the Gibbs free energy of a molecule, from its "noninteracting" fragments, as accurate as a few tenths of a kcal per mol. The latter observation seems to hold for peptides regardless of their length (1 Յ n Յ 8) or the level of theory applied.

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“…Several studies include alanine, [17][18][19][20] valine, 21 glutamic acid, [60][61][62][63][64][65][66][67] As performing quantum chemical calculations is inherently computationally expensive, approximations using analytical fitting methods have been widely used in the construction of PESs. 68,69 For instance, a fitting procedure based on the many-body expansion (MBE) method, 70 amplified by Varandas 71 is widely used in the so-called double many-body expansion (DMBE) method.…”

Section: Introductionmentioning

confidence: 99%

An improved two-rotor function for conformational potential energy surfaces of 20 amino acid diamides

et al. 2018

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Predicting the three-dimensional structure of a protein from its amino acid sequence requires a complete understanding of the molecular forces that influences the protein folding process. Each possible conformation has its corresponding potential energy, which characterizes its thermodynamic stability. This is needed to identify the primary intra- and inter-molecular interactions, so that we can reduce the dimensionality of the problem, and create a relatively simple representation of the system. Investigating this problem using quantum chemical methods produces accurate results; however, this also entails large computational resources. In this study, an improved two-rotor potential energy function is proposed to represent the backbone interactions in amino acids through a linear combination of a Fourier series and a mixture of Gaussian functions. This function is applied to approximate the 20 amino acid diamide Ramachandran-type PESs, and results yielded an average RMSE of 2.36 kJ mol−1, which suggest that the mathematical model precisely captures the general topology of the conformational potential energy surface. Furthermore, this paper provides insights on the conformational preferences of amino acid diamides through local minima geometries and energy ranges, using the improved mathematical model. The proposed mathematical model presents a simpler representation that attempts to provide a framework on building polypeptide models from individual amino acid functions, and consequently, a novel method for rapid but accurate evaluation of potential energies for biomolecular simulations.

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Peptide models. 1. Topology of selected peptide conformational potential energy surfaces (glycine and alanine derivatives)

Cited by 256 publications

References 0 publications

Development of Cyclic NGR Peptides with Thioether Linkage: Structure and Dynamics Determining Deamidation and Bioactivity

Development of Cyclic NGR Peptides with Thioether Linkage: Structure and Dynamics Determining Deamidation and Bioactivity

Stability issues of covalently and noncovalently bonded peptide subunits

An improved two-rotor function for conformational potential energy surfaces of 20 amino acid diamides

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