@article{17331,
  abstract     = {Amyloidosis are a group of diseases in which soluble proteins aggregate and deposit in fibrillar conformation extracellularly in tissues. The effectiveness of therapeutic strategies depends on the specific protein involved, being crucial to accurately determine its nature. Moreover, following the diagnosis, the search for the mutation within relatives allows the clinical advice. Here we report the precise diagnosis and explored the possible reasons of the structural pathogenicity for a renal amyloidosis related to a fibrinogen Aα-chain variant. Whole-exome sequencing and GATK calling pipeline were leveraged to characterize the protein variant present in a patient with kidney failure. Bioinformatics strategies were applied to suggest potential explanations of the variants aggregation. Our pipeline allowed the identification of a single-point variant of fibrinogen Aα-chain, which opened the possibility of curative transplantation. In silico structural analysis suggested that the pathogenicity of the variant may be attributed to a heightened susceptibility to yield a peptide prone to deposit as an oligomer with a β-sheet structure. Exploiting the comprehensive coverage of whole-genome sequencing, we managed to fill a vacant stage in the diagnosis of hereditary amyloidosis and to stimulate the advancement in biomedicine.},
  author       = {Cattaneo, Elizabeth R and Gisonno, Romina A and Abba, Martín C and Santana, Marianela and Rosú, Silvana A and Nucifora, Elsa and Aguirre, María A and Giordani, María C and Tricerri, M. Alejandra and Ramella, Nahuel A},
  issn         = {1097-0134},
  journal      = {Proteins: Structure, Function and Bioinformatics},
  number       = {12},
  pages        = {1366--1374},
  publisher    = {Wiley},
  title        = {{Hereditary amyloidosis: Insights into a fibrinogen A variant protein}},
  doi          = {10.1002/prot.26732},
  volume       = {92},
  year         = {2024},
}

@article{15268,
  abstract     = {Apolipoprotein A‐I (apoA‐I) has a key function in the reverse cholesterol transport. However, aggregation of apoA‐I single point mutants can lead to hereditary amyloid pathology. Although several studies have tackled the biophysical and structural consequences introduced by these mutations, there is little information addressing the relationship between the evolutionary and structural features that contribute to the amyloid behavior of apoA‐I. We combined evolutionary studies, in silico mutagenesis and molecular dynamics (MD) simulations to provide a comprehensive analysis of the conservation and pathogenic role of the aggregation‐prone regions (APRs) present in apoA‐I. Sequence analysis demonstrated that among the four amyloidogenic regions described for human apoA‐I, only two (APR1 and APR4) are evolutionary conserved across different species of Sarcopterygii. Moreover, stability analysis carried out with the FoldX engine showed that APR1 contributes to the marginal stability of apoA‐I. Structural properties of full‐length apoA‐I models suggest that aggregation is avoided by placing APRs into highly packed and rigid portions of its native fold. Compared to silent variants extracted from the gnomAD database, the thermodynamic and pathogenic impact of amyloid mutations showed evidence of a higher destabilizing effect. MD simulations of the amyloid variant G26R evidenced the partial unfolding of the alpha‐helix bundle with the concomitant exposure of APR1 to the solvent, suggesting an insight into the early steps involved in its aggregation. Our findings highlight APR1 as a relevant component for apoA‐I structural integrity and emphasize a destabilizing effect of amyloid variants that leads to the exposure of this region.},
  author       = {Gisonno, Romina A. and Masson, Tomas and Ramella, Nahuel A. and Barrera, Exequiel E. and Romanowski, Víctor and Tricerri, M. Alejandra},
  issn         = {1097-0134},
  journal      = {Proteins: Structure, Function, and Bioinformatics},
  keywords     = {Molecular Biology, Biochemistry, Structural Biology},
  number       = {1},
  pages        = {258--269},
  publisher    = {Wiley},
  title        = {{Evolutionary and structural constraints influencing apolipoprotein A‐I amyloid behavior}},
  doi          = {10.1002/prot.26217},
  volume       = {90},
  year         = {2022},
}

@article{4011,
  abstract     = {The size and shape of macromolecules such as proteins and nucleic acids play an important role in their functions. Prior efforts to quantify these properties have been based on various discretization or tessellation procedures involving analytical or numerical computations. In this article, we present an analytically exact method for computing the metric properties of macromolecules based on the alpha shape theory. This method uses the duality between alpha complex and the weighted Voronoi decomposition of a molecule. We describe the intuitive ideas and concepts behind the alpha shape theory and the algorithm for computing areas and volumes of macromolecules. We apply our method to compute areas and volumes of a number of protein systems. We also discuss several difficulties commonly encountered in molecular shape computations and outline methods to overcome these problems. (C) 1998 Wiley-Liss, Inc.},
  author       = {Liang, Jie and Edelsbrunner, Herbert and Fu, Ping and Sudhakar, Pamidighantam and Subramaniam, Shankar},
  issn         = {0887-3585},
  journal      = {Proteins: Structure, Function and Bioinformatics},
  number       = {1},
  pages        = {1 -- 17},
  publisher    = {Wiley-Blackwell},
  title        = {{Analytical shape computation of macromolecules: I. molecular area and volume through alpha shape}},
  doi          = {10.1002/(SICI)1097-0134(19981001)33:1<1::AID-PROT1>3.0.CO;2-O},
  volume       = {33},
  year         = {1998},
}

@article{4012,
  abstract     = {The structures of proteins are well-packed, yet they contain numerous cavities which play key roles in accommodating small molecules, or enabling conformational changes. From high-resolution structures it is possible to identify these cavities. We have developed a precise algorithm based on alpha shapes for measuring space-filling-based molecular models (such as van der Waals, solvent accessible, and molecular surface descriptions). We applied this method for accurate computation of the surface area and volume of cavities in several proteins. In addition, all of the atoms/residues Lining the cavities are identified, We use this method to study the structure and the stability of proteins, as well as to locate cavities that could contain structural water molecules in the proton transport pathway in the membrane protein bacteriorhodopsin.},
  author       = {Liang, Jie and Edelsbrunner, Herbert and Fu, Ping and Sudhakar, Pamidighantam and Subramaniam, Shankar},
  issn         = {0887-3585},
  journal      = {Proteins: Structure, Function and Bioinformatics},
  number       = {1},
  pages        = {18 -- 29},
  publisher    = {Wiley-Blackwell},
  title        = {{Analytical shape computation of macromolecules: II. Inaccessible cavities in proteins}},
  doi          = {10.1002/(SICI)1097-0134(19981001)33:1<18::AID-PROT2>3.0.CO;2-H},
  volume       = {33},
  year         = {1998},
}