pStab: prediction of stable mutants, unfolding curves, stability maps and protein electrostatic frustration

Gopi, Soundhararajan; Devanshu, Devanshu; Krishna, I. R. Praveen; Naganathan, Athi N.

doi:10.1093/bioinformatics/btx697

Cited by 15 publications

(13 citation statements)

References 10 publications

(11 reference statements)

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“…However, they are often underestimated or poorly predicted during enzyme engineering. TKSA-MC [18] and pStab [19] tools tackle this issue by assessing unfavorable electrostatic interactions and identifying charged hot-spot residues for mutagenesis.…”

Section: Engineering Protein Stabilitymentioning

confidence: 99%

Web-based tools for computational enzyme design

Marques

Planas-Iglesias

Damborský

2021

Current Opinion in Structural Biology

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Enzymes are on high demand for very diverse biotechnological applications. However, natural biocatalysts often need to be engineered for fine-tuning their properties towards the end applications, such as the activity, selectivity, stability to temperature or co-solvents, and solubility. Computational methods are increasingly used in this task, providing predictions that narrow down the space of possible mutations significantly and can enormously reduce the experimental burden. Many computational tools are available as web-based platforms, making them accessible to non-expert users.These platforms are typically user-friendly, contain walk-throughs, and do not require deep expertise and installations. Here we describe some of the most recent outstanding web-tools for enzyme engineering and formulate future perspectives in this field.

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Section: Engineering Protein Stabilitymentioning

confidence: 99%

Web-based tools for computational enzyme design

Marques

Planas-Iglesias

Damborský

2021

Current Opinion in Structural Biology

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“…Different software packages that calculate the electrostatic potential of proteins are available [ 151–153 ]. Apart from tools targeting protein stability such as the pStab web-server [ 154 ], there are not many tools that assess the effects of mutations on this vital feature.…”

Section: Tools For Predicting the Effects Of Mutationmentioning

confidence: 99%

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

Sequeiros-Borja

Surpeta

Brezovský

2020

Briefings in Bioinformatics

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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.

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“…This computational method consists in calculating the electrostatic free energy contribution of each ionizable residue of a protein using the Tanford-Kirkwood model with a correction that takes into account the solvent accessibility of these residues (TKSA). [17][18][19] All calculations are made for the protein in its native state (see further details in section 2). The difference between the approach presented here and that used by Makhatadze and colleagues lies in the way the ionizable states of the residues are sampled.…”

Section: Introductionmentioning

confidence: 99%

“…There is a set of servers that calculates the stability of proteins and their mutants based on electrostatic interaction energy. Some of These authors contributed equally to this work them use a modified Debye-Hückel (DH) formalism combined with a structure-based statistical mechanics model 19 to predict unfolding curves as a function of temperature. Others use the generalized Born models to estimate the pairwise contributions to electrostatic effects at molecular level.…”

Section: Introductionmentioning

confidence: 99%

TKSA‐MC: A web server for rational mutation through the optimization of protein charge interactions

et al. 2018

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The TKSAMC is a web server which calculates protein charge-charge interactions via the Tanford-Kirkwood Surface Accessibility model with the Monte Carlo method for sampling different protein protonation states. The optimization of charge-charge interactions via directed mutations has successfully enhanced the thermal stability of different proteins and could be a key to protein engineering improvement. The server presents the electrostatic free energy contribution of each polar-charged residue to the protein native state stability. Specific residues are suggested to be mutated for improving thermal stability. The choice of a residue is based on its fraction of side chain exposed to solvent and its positive free energy contribution, which tends to destabilize the protein native state. Any residue energy contribution can be shown as a function of pH condition. The web server is freely available at UNESP (São Paulo State University - DF/IBILCE): http://tksamc.df.ibilce.unesp.br and also on GitHub https://github.com/contessoto/tksamc.

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pStab: prediction of stable mutants, unfolding curves, stability maps and protein electrostatic frustration

Abstract: Supplementary data are available at Bioinformatics online.

Cited by 15 publications

References 10 publications

Web-based tools for computational enzyme design

Web-based tools for computational enzyme design

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

TKSA‐MC: A web server for rational mutation through the optimization of protein charge interactions

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