Aggrescan3D standalone package for structure-based prediction of protein aggregation properties

Kuriata, Aleksander; Iglesias, Valentín; Kurciński, Mateusz; Ventura, Salvador; Kmiecik, Sebastian

doi:10.1093/bioinformatics/btz143

Cited by 26 publications

(24 citation statements)

References 14 publications

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“…The concept should be first implemented in a structural predictor, where the intrinsic charge and lipophilic properties of amino acids would be modulated according to the protein conformational properties at any given pH. This step will be analogous to the evolution of AGGRESCAN [14] into our structural A3D aggregation predictor [70][71][72] and thus, perfectly attainable.…”

Section: Discussionmentioning

confidence: 99%

pH-Dependent Aggregation in Intrinsically Disordered Proteins Is Determined by Charge and Lipophilicity

Santos

Iglesias

Santos-Suárez

et al. 2020

Cells

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Protein aggregation is associated with an increasing number of human disorders and premature aging. Moreover, it is a central concern in the manufacturing of recombinant proteins for biotechnological and therapeutic applications. Nevertheless, the unique architecture of protein aggregates is also exploited by nature for functional purposes, from bacteria to humans. The relevance of this process in health and disease has boosted the interest in understanding and controlling aggregation, with the concomitant development of a myriad of algorithms aimed to predict aggregation propensities. However, most of these programs are blind to the protein environment and, in particular, to the influence of the pH. Here, we developed an empirical equation to model the pH-dependent aggregation of intrinsically disordered proteins (IDPs) based on the assumption that both the global protein charge and lipophilicity depend on the solution pH. Upon its parametrization with a model IDP, this simple phenomenological approach showed unprecedented accuracy in predicting the dependence of the aggregation of both pathogenic and functional amyloidogenic IDPs on the pH. The algorithm might be useful for diverse applications, from large-scale analysis of IDPs aggregation properties to the design of novel reversible nanofibrillar materials.

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Section: Discussionmentioning

confidence: 99%

pH-Dependent Aggregation in Intrinsically Disordered Proteins Is Determined by Charge and Lipophilicity

Santos

Iglesias

Santos-Suárez

et al. 2020

Cells

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“…Moreover, CABS-flex method is successfully used in Aggrescan3D method [15][16][17][18] to predict the influence of protein flexibility on protein aggregation properties, and in CABS-dock method for simulations of protein flexibility during peptide molecular docking [19][20][21][22]. CABS-flex method is presently available as the CABS-flex 2.0 web server [3] (http://biocomp.chem.uw.edu.pl/CABSflex2) and the standalone package [4].…”

Section: Materials 21 Cabs-flex Methodsmentioning

confidence: 99%

Protocols for fast simulations of protein structure flexibility using CABS-flex and SURPASS

Badaczewska-Dawid

Koliński

Kmiecik

2019

Preprint

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Conformational flexibility of protein structures can play an important role in protein function. The flexibility is often studied using computational methods, since experimental characterization can be difficult. Depending on protein system size; computational tools may require large computational resources or significant simplifications in the modeled systems to speed-up calculations. In this work, we present the protocols for efficient simulations of flexibility of folded protein structures that use coarse-grained simulation tools of different resolutions: medium, represented by CABS-flex, and low, represented by SUPRASS. We test the protocols using a set of 140 globular proteins and compare the results with structure fluctuations observed in MD simulations, ENM modeling and NMR ensembles. As demonstrated, CABS-flex predictions show high correlation to experimental and MD simulation data, while SURPASS is less accurate but promising in terms of future developments.

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“…This is possible in A3D Dynamic Mode that uses the CABS-flex method for the fast simulations of flexibility of globular proteins 5,6 . Since 2015, A3D has been successfully used in many studies aimed at enhancing protein solubility 7-10 . In 2019, following the users requests, we introduced the updated 2.0 version of the A3D web server 11 and A3D standalone application package 12 . The A3D 2.0 web server offers several new functionalities like simultaneous prediction of changes in protein solubility and stability upon mutation, automated mutations tool that identifies high scoring residues and suggests protein variants with optimized solubility, dynamic mode calculations for large and multimeric proteins, a REST-ful service to incorporate A3D calculations in automatic pipelines, and a new, enhanced web server interface.…”

Section: Introductionmentioning

confidence: 99%

Protocols for rational design of protein solubility and aggregation properties using Aggrescan3D standalone

Kuriata

Badaczewska-Dawid

Pujols

et al. 2020

Preprint

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SummaryProtein aggregation is a major hurdle in the development and manufacturing of protein-based therapeutics. Development of aggregation-resistant and stable protein variants can be guided by rational redesign using computational tools. Here, we describe the architecture and functionalities of the Aggrescan3D (A3D) standalone package for the rational design of protein solubility and aggregation properties based on three-dimensional protein structures. We present the case studies of the three therapeutic proteins, including antibodies, exploring the practical use of the A3D standalone tool. The case studies demonstrate that protein solubility can be easily improved by the A3D prediction of non-destabilizing amino acid mutations at the protein surfaces.

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Aggrescan3D standalone package for structure-based prediction of protein aggregation properties

Cited by 26 publications

References 14 publications

pH-Dependent Aggregation in Intrinsically Disordered Proteins Is Determined by Charge and Lipophilicity

pH-Dependent Aggregation in Intrinsically Disordered Proteins Is Determined by Charge and Lipophilicity

Protocols for fast simulations of protein structure flexibility using CABS-flex and SURPASS

Protocols for rational design of protein solubility and aggregation properties using Aggrescan3D standalone

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