Significance of Root-Mean-Square Deviation in Comparing Three-dimensional Structures of Globular Proteins

Maiorov, Vladimir N.; Crippen, Gordon M.

doi:10.1006/jmbi.1994.1017

Cited by 410 publications

(279 citation statements)

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“…For our calmodulin simulations, the progress coordinate was chosen to be the negative of the DRMSD (see SI Text) (69) to the Holo state. The simulation starts from the Apo state and progresses toward Holo.…”

Section: Methodsmentioning

confidence: 99%

Efficient and verified simulation of a path ensemble for conformational change in a united-residue model of calmodulin

Zhang

Jasnow

Zuckerman

2007

Proc. Natl. Acad. Sci. U.S.A.

123

165

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The computational sampling of rare, large-scale, conformational transitions in proteins is a well appreciated challenge-for which a number of potentially efficient path-sampling methodologies have been proposed. Here, we study a large-scale transition in a united-residue model of calmodulin using the ''weighted ensemble'' (WE) approach of Huber and Kim. Because of the model's relative simplicity, we are able to compare our results with bruteforce simulations. The comparison indicates that the WE approach quantitatively reproduces the brute-force results, as assessed by considering (i) the reaction rate, (ii) the distribution of event durations, and (iii) structural distributions describing the heterogeneity of the paths. Importantly, the WE method is readily applied to more chemically accurate models, and by studying a series of lower temperatures, our results suggest that the WE method can increase efficiency by orders of magnitude in more challenging systems.transition path ͉ path sampling ͉ weighted ensemble ͉ conformational transition

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Section: Methodsmentioning

confidence: 99%

Efficient and verified simulation of a path ensemble for conformational change in a united-residue model of calmodulin

Zhang

Jasnow

Zuckerman

2007

Proc. Natl. Acad. Sci. U.S.A.

123

165

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“…The RMSD analysis, as a measure of flexibility and folding [15][16][17], was conducted for all of the PAMAM dendrimer structures. A plateau was seen after the first 1400 ps (Fig.…”

Section: <Figure 4>mentioning

confidence: 99%

Structural studies of biologically active glycosylated polyamidoamine (PAMAM) dendrimers

et al. 2010

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The partial modification of carboxylic acid terminated polyamidoamine (PAMAM) dendrimers with glucosamine has been reported to give dendrimer glucosamine conjugates novel immuno-modulatory and anti-angiogenic properties. Experimental analysis of these glycosylated dendrimers showed that, on average, eight glucosamine molecules were covalently bound to each dendrimer. In order to better understand the surface loading and distribution of these glucosamine molecules, molecular reactivity was determined by evaluation of electronic properties using frontier molecular orbital theory (FMOT) and molecular dynamics simulations. It was shown that the surface loading and distribution of the zero length amide bond conjugated glucosamine molecules was determined by both electronic effects and by the different dynamic conformations adopted by the modified dendrimer during the incremental addition of glucosamine. Importantly, the structural features and the dynamic behavior of the partially glycosylated generation 3.5 PAMAM dendrimer showed that its flexibility and its polarity changed with the incremental addition of glucosamine. These 2 peripheral glucosamine molecules remained available on the dendrimer"s surface for interaction with the biological target.

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“…a deletion of two residues, are shown in Table 2. These fragments were fitted onto the defined anchor groups in the AB loop and showed distance matrix errors [19] below 1.3 Å . Proceeding this way, we obtained several reasonable backbone conformations were obtained for AB loops truncated by two residues (Fig.…”

Section: Possible Length and Conformations Of Truncated Ab Loopsmentioning

confidence: 99%

Interferon‐γ variants with deletions in the AB surface loop

Waschütza

Dengler

Villmann

et al. 1998

European Journal of Biochemistry

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The receptor-binding AB loop of recombinant human interferon-γ (IFN-γ) has multiple contacts with the extracellular part of the IFN-γ receptor A chain (IFN-γRA). We explored the possible length of truncated AB loops and their conformations by molecular modelling. Deletions of two amino acids at the tip of the loop were tolerated in the model without van der Waals collisions of the AB loop with helix F. Based on these modelling results, two deletion mutants were constructed by overlap-extension PCR mutagenesis: des-(A23, D24)-IFN-γ and des-(N25, G26)-IFN-γ. Both mutations were tolerated by the folding pattern of recombinant human IFN-γ, as proved by CD spectroscopy. The stability of both mutants against cosolvent-induced unfolding was equal to that of wild-type IFN-γ. In contrast to the biophysical similarities of wild-type and mutant IFN-γ proteins, the biological activities of both mutants dropped significantly. Antiviral activity and human leucocyte antigen (HLA)-DR induction of des-(N25, G26)-IFN-γ was 10% that of wild-type activity. des-(A23, D24)-IFN-γ had only 1% remaining activity. Receptor-binding experiments confirmed that both deletions had a negative influence on the affinity of recombinant human IFN-γ to its cellular receptor. We conclude from this combined molecular modelling and mutagenesis experiments, that the reduced flexibility of the truncated AB loop abrogates the possibility of the formation of a 3 10 helix in the receptor-bound state as observed in the X-ray structure of the IFN-γRAϪIFN-γ complex.Keywords : interferon-γ; protein loops; computer modelling. 17 to 27. With an end-to-end distance of 15 Å (distance between the C A atoms of Ala17 and Thr27), it belongs to the class of Ω loops [7].The goal of our study was to examine the tolerance of the receptor-binding loop of recombinant human IFN-γ for deletions. An alignment of the AB-loop sequences from different species displays a one amino acid gap in mouse IFN-γ at Ala23 in the human sequence ( Table 1). This indicates a length variability in this region. Furthermore, the amino acid sequence of the AB loop determines the high species specificity of the cytokine [8]. MATERIALS AND METHODSModelling deletions in human IFN-γ. For computer modelling and documentation, the software packages BRAGI [9] and SYBYL (Tripos Associates Inc.) were used on a HP series 9000 model 735/99 workstation and on a Silicon Graphics Indigo 2 workstation, respectively. The starting model of recombinant human IFN-γ is based on the C A coordinates of the corresponding crystal structure (PDB code 1hig [2]) and has been described in an earlier report [6]. Deletions were constructed using a database search procedure [10]: a non-redundant fragment database, derived by hierarchical clustering (HCAPD database) is searched for suitable loops according to geometrical criteria derived from defined anchor groups in the template protein. The conformations of the highest ranked loops were inspected manually, and one loop fragment was selected. This selection was used to sim-

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Significance of Root-Mean-Square Deviation in Comparing Three-dimensional Structures of Globular Proteins

Cited by 410 publications

References 0 publications

Efficient and verified simulation of a path ensemble for conformational change in a united-residue model of calmodulin

Efficient and verified simulation of a path ensemble for conformational change in a united-residue model of calmodulin

Structural studies of biologically active glycosylated polyamidoamine (PAMAM) dendrimers

Interferon‐γ variants with deletions in the AB surface loop

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