SPROUTS: a database for the evaluation of protein stability upon point mutation

Lonquety, Mathieu; Lacroix, Zoé; Παπανδρεου, Νικολαοσ; Chomilier, Jacques

doi:10.1093/nar/gkn704

Cited by 30 publications

(30 citation statements)

References 23 publications

(31 reference statements)

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“…The interface provides access to 385 protein sequences with each position mutated by the five algorithms for the 19 amino acids, thus leading to 6,765,045 different calculations. Several query and visualization modes have been implemented for an easier overview and a quick analysis of the results (Lonquety et al, 2008b). …”

Section: Stability Scorementioning

confidence: 99%

Prediction of Stability upon Point Mutation in the Context of the Folding Nucleus

Lonquety

Chomilier²,

Παπανδρεου³

et al. 2010

OMICS: A Journal of Integrative Biology

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Proteins come in all shapes and sizes. Although it is possible to predict with reasonable success their structure from their sequence, the process of folding a chain of amino acids into its tertiary structure remains partially understood. This article addresses several characteristics pertaining to protein folding. The development of the Most Interacting Residues (MIR) algorithm, which dynamically simulates the early folding events, permits a reasonable ab initio prediction of the deeply buried critical residues involved in the formation of the protein core. The analysis of MIR positions with respect to protein 3D topology, in particular, to fragments called Tightened End Fragments (TEF) that might be good candidate for autonomous folding units, suggests that they are also essential for defining core stability. To validate this hypothesis, this study measures the sensitivity of MIR residues to point mutations. It is performed on a set of 385 proteins from a database that contains stability data calculated with five different algorithms. Tools have been developed to help the analysis and a consensus of the five methods is proposed. It results that positions predicted both as a MIR and a minimum of stability for the consensus are good candidates for the folding nucleus, and consequently their mutations may be hazardous.

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Section: Stability Scorementioning

confidence: 99%

Prediction of Stability upon Point Mutation in the Context of the Folding Nucleus

Lonquety

Chomilier²,

Παπανδρεου³

et al. 2010

OMICS: A Journal of Integrative Biology

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“…The standalone MIR 1.0 implementation was first made available online as a part of the RPBS server in 2005 [13]. The SPROUTS submission server [12] uses the MIR2.2, with a browser client side extension for SMIR3.10 algorithms, implementation (in Fortran) for server side simulation, and provides a Javascript front end for interactive analysis and smoothing [15]. It may be accessed at http://sprouts.rpbs.univ-paris-diderot.fr/mir.…”

Section: Resultsmentioning

confidence: 99%

“…A second promising area resides in integrating MIR with stability analyses to better predict the impact of mutations on protein structure [10,38,39]. We will investigate how the consensus method consisting of the average of various stability analyses currently made available in SPROUTS [12] can be improved for the prediction of the dramatic impact of mutation of protein structures with MIR.…”

Section: Discussionmentioning

confidence: 99%

“…Protein stability can be examined in terms of ΔΔG values, representing the change in free energy difference between a wild type and a mutant. One feature of SPROUTS is a repository of ΔΔG values predicted by a suite of eight tools for every possible amino acid substitution at every position of a protein [12]. SPROUTS includes the ability to graph this in terms of a so-called impact count.…”

Section: Stabilitymentioning

confidence: 99%

“…There is a statistical correspondence between MIRs and stable positions [11]. The MIR algorithm is now available online as part of Structural Prediction for pRotein fOlding UTility System (SPROUTS) [12], hosted by Ressource Parisienne en Bioinformatique Structurale (RPBS) [13]. It may be accessed at http://sprouts.rpbs.univ-parisdiderot.fr/.…”

Section: Introductionmentioning

confidence: 99%

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Protein intrachain contact prediction with most interacting residues (MIR)

Acuna

Lacroix

Παπανδρεου

et al. 2014

Bio-Algorithms and Med-Systems

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The transition state ensemble during the folding process of globular proteins occurs when a sufficient number of intrachain contacts are formed, mainly, but not exclusively, due to hydrophobic interactions. These contacts are related to the folding nucleus, and they contribute to the stability of the native structure, although they may disappear after the energetic barrier of transition states has been passed. A number of structure and sequence analyses, as well as protein engineering studies, have shown that the signature of the folding nucleus is surprisingly present in the native three-dimensional structure, in the form of closed loops, and also in the early folding events. These findings support the idea that the residues of the folding nucleus become buried in the very first folding events, therefore helping the formation of closed loops that act as anchor structures, speed up the process, and overcome the Levinthal paradox. We present here a review of an algorithm intended to simulate in a discrete space the early steps of the folding process. It is based on a Monte Carlo simulation where perturbations, or moves, are randomly applied to residues within a sequence. In contrast with many technically similar approaches, this model does not intend to fold the protein but to calculate the number of non-covalent neighbors of each residue, during the early steps of the folding process. Amino acids along the sequence are categorized as most interacting residues (MIRs) or least interacting residues. The MIR method can be applied under a variety of circumstances. In the cases tested thus far, MIR has successfully identified the exact residue whose mutation causes a switch in conformation. This follows with the idea that MIR identifies residues that are important in the folding process. Most MIR positions correspond to hydrophobic residues; correspondingly, MIRs have zero or very low accessible surface area. Alongside the review of the MIR method, we present a new postprocessing method called smoothed MIR (SMIR), which refines the original MIR method by exploiting the knowledge of residue hydrophobicity. We review known results and present new ones, focusing on the ability of MIR to predict structural changes, secondary structure, and the improved precision with the SMIR method.

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Impact of a Point Mutation in a Protein Structure

Carpentier¹,

Chomilier²

2021

Systematics and the Exploration of Life

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SPROUTS: a database for the evaluation of protein stability upon point mutation

Cited by 30 publications

References 23 publications

Prediction of Stability upon Point Mutation in the Context of the Folding Nucleus

Prediction of Stability upon Point Mutation in the Context of the Folding Nucleus

Protein intrachain contact prediction with most interacting residues (MIR)

Impact of a Point Mutation in a Protein Structure

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