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A topological analysis of molecular electrostatic potential on van der Waals surfaces for histamine and 4‐substituted derivatives as H 2 ‐receptor agonists
Author(s) -
Arteca Gustavo A.,
HernándezLaguna Alfonso,
Rández Juan J.,
Smeyers Yves G.,
Mezey Paul G.
Publication year - 1991
Publication title -
journal of computational chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.907
H-Index - 188
eISSN - 1096-987X
pISSN - 0192-8651
DOI - 10.1002/jcc.540120608
Subject(s) - electrostatics , van der waals force , chemistry , molecule , biomolecule , topology (electrical circuits) , surface (topology) , context (archaeology) , static electricity , molecular recognition , van der waals surface , chemical physics , computational chemistry , physics , van der waals radius , quantum mechanics , mathematics , geometry , paleontology , biochemistry , organic chemistry , combinatorics , biology
The molecular electrostatic potential is an important property for characterizing chemical reactivity and the interactions between biomolecules. A joint description of the molecular electrostatics and the molecular shape in 3‐space is more complete than the one provided by only the electrostatics. The characterization of the interrelations between the shape features of a formal “molecular surface” and electrostatic potential is of importance in assessing the degree of similarity within a family of molecules. In this work, we have applied a recently developed topological technique to characterize these aspects of the molecular shape. The approach allows one to calculate simple and concise shape codes which can be used for rationalizing structure‐activity correlations. These shape codes are related to topological invariants which characterize the topological structure given to the molecular surface by the electrostatic potential. In this work the molecules of interest are a series of four agonists of the H 2 ‐receptor of histamine with very different pharmacological activities. We have analyzed the electrostatics on the fused‐sphere (van der Waals) surfaces of these compounds for a number of conformations. Some structural properties and the shape descriptions have been found to correlate with the activity. The results are discussed in the context of the current H 2 ‐receptor models.