Analysis of molecular recognition: Steric electrostatic and hydrophobic complementarity

Abstract

We discuss three important aspects of molecular recognition: steric, electrostatic and hydrophobic. Steric fit means that interacting atoms may not approach each other beyond their van der Waals radii and, simultaneously, crevices should be filled as densely as possible. Electrostatic fit requires the maximum ionic and polar (hydrogen bond or other) interaction between host and guest atoms while the hydrophobic fit corresponds to the association trend between apolar groups in an aqueous medium. Space-filling models, obtained by molecular graphics, illustrate steric complementarity while we use molecular electrostatic potentials (MEPs) and fields (MEFs) to investigate electrostatic and hydrophobic matching. Molecular regions with negative and positive MEPs attract and repel a positive probe charge, respectively, so we consider them as attracting each other. Furthermore we postulate that regions with MEFs of similar magnitude tend to associate more strongly than those with very different fields (similis simili gaudet principle). We apply the above rules to the study of complementarity in the trypsin-BPTI complex and in a crystalline association between styrene epoxide as guest and a camphor-based anthracene derivative as host. We discuss molecular similarity on the same footing as complementarity and give some examples on the application of the concept to the rationalization of relative strengths of trypsin inhibitors.

Radial scan of the molecular electrostatic potential of RNA double helices: An application to the enzyme-tRNA recognition

“…Although they were not able to find them, they showed for eight base pairs that similarity of the electrostatic potential in the major groove was reflected in the aminoacylation activity, i.e., electrostatically similar base pairs had similar activities. These findings agree with the notion of electrostatic complementarity or the electrostatic lock, as it was previously proposed by Ná ray-Szabó [6][7][8][9]. He proposed that a more complete key-andlock model to recreate enzyme-substrate interaction has to consider the electrostatic fit as well as the geometrical fit, since the enzyme has to find its electrostatic counterpart in the binding site in order to allow maximum interaction between molecules.…”

“…However, as all aminoacylation activities were obtained with the same enzyme (E. coli AlaRS) we expect that base pairs with similar MEP will have similar electrostatic complementarity with the enzyme, and therefore they will induce similar activities, as has been suggested by Ná ray-Szabó [8,9]. Additionally, since the AlaRS-tRNA Ala interactions are expected to be similar to those observed in the ThrRS-tRNA Thr complex [28], specially in the interaction involving the acceptor stem, we assume that performing the same analysis over this second system would serve as a guide to evaluate the results obtained for the alanine system.…”

“…He proposed that a more complete key-andlock model to recreate enzyme-substrate interaction has to consider the electrostatic fit as well as the geometrical fit, since the enzyme has to find its electrostatic counterpart in the binding site in order to allow maximum interaction between molecules. Several works based on this idea showed that a better biological recognition is obtained when a better electrostatic complementarity is reached [6][7][8][9][10][11][12][13][14][15].…”

Homology modelling and protein structure based functional analysis of five cucumovirus coat proteins

“…In the literature, there are also examples showing that the replacement of one or two residues in the CP can alter the infectivity of the virus, leading to different symptoms or a noninfectious virus becomes infectious on a special host plant [3,6,19,20,21]. These cases are analyzed in this paper and we discuss the experimental results on the basis of structural and functional aspects using spatial, electrostatic and hydrophobic determinants of the compared CPs [8]. Additionally, we make predictions for the other cucumovirus CPs.…”

Biomimetic Molecular Recognition Elements for Chemical Sensing

“…Throughout biological and biomimetic systems, receptive sites often present themselves as a concave surface laden with acids, bases, amino acids, metal ions, and so on to offer noncovalent interactions in a structurally controlled space to receive the complementary molecular guest [21]. From a steric viewpoint, a complementary guest implies that the van der Waals radii of the guest molecule's atoms cannot go beyond that of the host and correspondingly should serve to fill the host cavity as densely as possible [22]. Although complete structural complementarity may not be required for molecular recognition [23], this section considers such molecular recognition system in order to begin to explore the elements and thermodynamics of the binding event as well as the means of analyzing and quantifying the host-guest molecular interaction.…”