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Protein Quadratic Indices of the “Macromolecular Pseudograph’s α-Carbon Atom Adjacency Matrix”. 1. Prediction of Arc Repressor Alanine-mutant’s Stability

Author(s): Yovani Marrero Ponce | Ricardo Medina Marrero | Eduardo A. Castro | Ronal Ramos de Armas | Humberto González Díaz | Vicente Romero Zaldivar | Francisco Torrens

Journal: Molecules ISSN 1420-3049
Volume: 9; Issue: 12; Start page: 1124; Date: 2004;
Original page

Keywords: Protein Stability | Arc Repressor | Alanine-Substitution Mutant | TOMOCOMD Software | Protein Quadratic Indices | QSPR.

ABSTRACT
This report describes a new set of macromolecular descriptors of relevance toprotein QSAR/QSPR studies, protein’s quadratic indices. These descriptors are calculatedfrom the macromolecular pseudograph’s α-carbon atom adjacency matrix. A study of theprotein stability effects for a complete set of alanine substitutions in Arc repressorillustrates this approach. Quantitative Structure-Stability Relationship (QSSR) modelsallow discriminating between near wild-type stability and reduced-stability A-mutants. Alinear discriminant function gives rise to excellent discrimination between 85.4% (35/41)and 91.67% (11/12) of near wild-type stability/reduced stability mutants in training andtest series, respectively. The model’s overall predictability oscillates from 80.49 until82.93, when n varies from 2 to 10 in leave-n-out cross validation procedures. This valuestabilizes around 80.49% when n was