Protein interaction property similarity analysis

Abstract

ABSTRACT:We describe how similarity indices may be applied to semiquantitatively compare the molecular interaction fields, such as electrostatic and hydrophobic potentials, of proteins. We then review ways in which this approach has been used to investigate protein interaction properties in diverse applications ranging from in-depth comparison of pairs of proteins to large-scale analysis of hundreds of modeled protein structures.

Regulation of the Activity of Lactate Dehydrogenases from Four Lactic Acid Bacteria

“…Comparison of the Allosteric Binding Sites-The Protein Interaction Property Similarity Analysis (PIPSA) tool allows comparison of protein interaction fields (in this work electrostatic potentials) in the intersection of the "skins" of two superimposed structures (27). The "skin" region is defined as the volume remaining after exclusion of the region within the protein surface accessible to a probe of radius ϭ 3 Å and the region outside the protein surface accessible to a probe of radius ϩ ␦ (␦ ϭ 4 Å).…”

Automated computational framework for the analysis of electrostatic similarities of proteins

“…We have also tested distance measures based on previously presented scalar products. [30][31][32][33][34] However, the presented here ANDs performed better in cluster classification with regard to visual inspection of the spatial distributions of electrostatic potentials. This is mainly because the difference and normalization is performed at each grid point, before summation.…”

Application of New Multiresolution Methods for the Comparison of Biomolecular Electrostatic Properties in the Absence of Global Structural Similarity

“…Many methods use the fact that solutions to the PB equation away from the location of point charges are square-integrable [26] implying finite inner products: (1) and norms: (2) Similarity indices have been popular in QSAR studies [12,13,24] and the study of biomolecular electrostatics [53,8]. The most popular metrics were introduced by Hodgkin et al [24,12] and Carbo S C (u,v) [13]: (4) As can be seen from their definitions, these indices only differ by their choice of normalization; the Hodgkin index offers the advantage of distinguishing between functions which differ by a constant multiple, while the Carbo index provides a natural measure of the extent of orthogonality between two functions.…”

“…In both cases, these indices are essentially modified L 2 (Ω) inner products which return 1 for identical functions, -1 for functions which are different only by a constant multiple of 1, and 0 for orthogonal (i.e., unrelated) functions. To prevent numerical instability due to the singular nature of the electrostatic potential near atomic point charges, the domain of integration (Ω) is often chosen to be some space outside the union of biomolecular volumes [8,53,54].…”

“…Much of this work includes identification of functionally-relevant residues in biomolecules by looking at electrostatic destabilization of conserved residues [18], highly shifted pK a values [44], clusters of charged residues [59], protein-membrane interactions [40], and other structural characteristics [55]. Other research has focused on comparisons of electrostatic potentials including global analyses of the biomolecular structure [38,9,40,51,37,30,36,47,43,8,53,34,46,35,52] both in threedimensional space over the entire biomolecular structure and at localized regions such as active sites [52,6,22]. While the past characterization of electrostatic properties of biomolecules has provided insight into a variety of biomolecular properties, previous applications focused only on a few quantitative measures of electrostatic properties and, with a few exceptions [8,57], limited their studies to relatively small numbers of biomolecules.…”