Mutantelec: An <i>In Silico</i> mutation simulation platform for comparative electrostatic potential profiling of proteins

Valdebenito-Maturana, Braulio; Reyes-Suárez, José Antonio; Henriquez, Jaime; Holmes, David S.; Quatrini, Raquel; Pohl, Ehmke; Arenas-Salinas, Mauricio

doi:10.1002/jcc.24712

Cited by 6 publications

(5 citation statements)

References 49 publications

(86 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Changes in electrostatic potential of each protein, which is responsible for catalytic activity in many enzymes, were measured using the MutantElec webserver (http://structuralbio.utalca.cl/mutantelec; last accessed May 11, 2018. Valdebenito-Maturana et al. 2017).…”

Section: Methodsmentioning

confidence: 99%

Phylotranscriptomic Insights into the Diversification of EndothermicThunnusTunas

Ciezarek

Osborne

Shipley

et al. 2018

Molecular Biology and Evolution

View full text Add to dashboard Cite

Birds, mammals, and certain fishes, including tunas, opahs and lamnid sharks, are endothermic, conserving internally generated, metabolic heat to maintain body or tissue temperatures above that of the environment. Bluefin tunas are commercially important fishes worldwide, and some populations are threatened. They are renowned for their endothermy, maintaining elevated temperatures of the oxidative locomotor muscle, viscera, brain and eyes, and occupying cold, productive high-latitude waters. Less cold-tolerant tunas, such as yellowfin tuna, by contrast, remain in warm-temperate to tropical waters year-round, reproducing more rapidly than most temperate bluefin tuna populations, providing resiliency in the face of large-scale industrial fisheries. Despite the importance of these traits to not only fisheries but also habitat utilization and responses to climate change, little is known of the genetic processes underlying the diversification of tunas. In collecting and analyzing sequence data across 29,556 genes, we found that parallel selection on standing genetic variation is associated with the evolution of endothermy in bluefin tunas. This includes two shared substitutions in genes encoding glycerol-3 phosphate dehydrogenase, an enzyme that contributes to thermogenesis in bumblebees and mammals, as well as four genes involved in the Krebs cycle, oxidative phosphorylation, β-oxidation, and superoxide removal. Using phylogenetic techniques, we further illustrate that the eight Thunnus species are genetically distinct, but found evidence of mitochondrial genome introgression across two species. Phylogeny-based metrics highlight conservation needs for some of these species.

show abstract

Section: Methodsmentioning

confidence: 99%

Phylotranscriptomic Insights into the Diversification of EndothermicThunnusTunas

Ciezarek

Osborne

Shipley

et al. 2018

Molecular Biology and Evolution

View full text Add to dashboard Cite

show abstract

“…The physicochemical descriptors evaluated were the differences in electrostatic potential (EP) between residues from each mutated protein and residues from the WT-PZAse and the sum of all differences in electrostatic potential in the entire protein. The MutantElec server [ 68 ] was used to calculate EPs, this server uses an Adaptive Poisson-Boltzmann Solver (APBS) to analyze the effect of solvents in proteins and as input requires the dielectric constant of protein (Ɛ protein ) and water (Ɛ water ) at a fixed temperature. We assumed a value of Ɛ protein of 4 as a mean for proteins and calculated Ɛ water = 74.1522 at T = 37°C (which represents lung temperature) as previously reported [ 69 ].…”

Section: Methodsmentioning

confidence: 99%

Prediction of Mycobacterium tuberculosis pyrazinamidase function based on structural stability, physicochemical and geometrical descriptors

et al. 2020

View full text Add to dashboard Cite

Background Pyrazinamide is an important drug against the latent stage of tuberculosis and is used in both first- and second-line treatment regimens. Pyrazinamide-susceptibility test usually takes a week to have a diagnosis to guide initial therapy, implying a delay in receiving appropriate therapy. The continued increase in multi-drug resistant tuberculosis and the prevalence of pyrazinamide resistance in several countries makes the development of assays for prompt identification of resistance necessary. The main cause of pyrazinamide resistance is the impairment of pyrazinamidase function attributed to mutations in the promoter and/or pncA coding gene. However, not all pncA mutations necessarily affect the pyrazinamidase function. Objective To develop a methodology to predict pyrazinamidase function from detected mutations in the pncA gene. Methods We measured the catalytic constant (k cat ), K M , enzymatic efficiency, and enzymatic activity of 35 recombinant mutated pyrazinamidase and the wild type (Protein Data Bank ID = 3pl1). From all the 3D modeled structures, we extracted several predictors based on three categories: structural stability (estimated by normal mode analysis and molecular dynamics), physicochemical, and geometrical characteristics. We used a stepwise Akaike’s information criterion forward multiple log-linear regression to model each kinetic parameter with each category of predictors. We also developed weighted models combining the three categories of predictive models for each kinetic parameter. We tested the robustness of the predictive ability of each model by 6-fold cross-validation against random models. Results The stability, physicochemical, and geometrical descriptors explained most of the variability (R 2 ) of the kinetic parameters. Our models are best suited to predict k cat , efficiency, and activity based on the root-mean-square error of prediction of the 6-fold cross-validation. Conclusions This study shows a quick approach to predict the pyrazinamidase function only from the pncA sequence when point mutations are present. This can be an important tool to detect pyrazinamide resistance.

show abstract

“…The DynaMut server aims to rapidly evaluate changes in protein dynamics and stability after mutation [ 61 ]. The study of modifications in electrostatic potential upon mutation is the domain of the Mutantelec tool [ 62 ] and the analysis of electrostatic structures of proteins (AESOP) library [ 63 ]. Finally, the BioStructMap integrates data from various sources to help harness the knowledge for the next round of engineering [ 66 ].…”

Section: Tools For Predicting the Effects Of Mutationmentioning

confidence: 99%

“…To overcome this deficiency, the Mutantelec web-server was developed to enable evaluation of the effects that mutations have on electrostatic potential [ 62 ]. Additionally, the effects of phosphorylation of serine, threonine and tyrosine can be assessed, broadening the type of analysis that can be performed.…”

Section: Tools For Predicting the Effects Of Mutationmentioning

confidence: 99%

“…Additionally, the web-server allows for download of 3D structures and electrostatic maps to visualize in PyMOL (Schrödinger, LLC., USA, http: // www.pymol.org/ ) or VMD [ 157 ]. The p53 protein was analyzed with Mutantelec to explain the effects of Arg249 mutations shown to inactivate the protein function [ 62 ].…”

Section: Tools For Predicting the Effects Of Mutationmentioning

confidence: 99%

See 1 more Smart Citation

Recent advances in user-friendly computational tools to engineer protein function

Sequeiros-Borja

Surpeta

Brezovský

2020

Briefings in Bioinformatics

View full text Add to dashboard Cite

Progress in technology and algorithms throughout the past decade has transformed the field of protein design and engineering. Computational approaches have become well-engrained in the processes of tailoring proteins for various biotechnological applications. Many tools and methods are developed and upgraded each year to satisfy the increasing demands and challenges of protein engineering. To help protein engineers and bioinformaticians navigate this emerging wave of dedicated software, we have critically evaluated recent additions to the toolbox regarding their application for semi-rational and rational protein engineering. These newly developed tools identify and prioritize hotspots and analyze the effects of mutations for a variety of properties, comprising ligand binding, protein–protein and protein–nucleic acid interactions, and electrostatic potential. We also discuss notable progress to target elusive protein dynamics and associated properties like ligand-transport processes and allosteric communication. Finally, we discuss several challenges these tools face and provide our perspectives on the further development of readily applicable methods to guide protein engineering efforts.

show abstract

Mutantelec: An In Silico mutation simulation platform for comparative electrostatic potential profiling of proteins

Cited by 6 publications

References 49 publications

Phylotranscriptomic Insights into the Diversification of EndothermicThunnusTunas

Phylotranscriptomic Insights into the Diversification of EndothermicThunnusTunas

Prediction of Mycobacterium tuberculosis pyrazinamidase function based on structural stability, physicochemical and geometrical descriptors

Recent advances in user-friendly computational tools to engineer protein function

Contact Info

Product

Resources

About