F. Manaut

Automatic search for maximum similarity between molecular electrostatic potential distributions

SummaryA new computer program has been developed to automatically obtain the relative position of two molecules in which the similarity between molecular electrostatic-potential distributions is greatest. These distributions are considered in a volume around the molecules, and the similarity is measured by the Spearman rank coefficient. The program has been tested using several pairs of molecules: water vs. water; phenylethylamine and phenylpropylamine vs. benzylamine; and methotrexate vs. dihydrofolic acid.

MEPSIM: A computational package for analysis and comparison of molecular electrostatic potentials

SummaryMEPSIM is a computational system which allows an integrated computation, analysis, and comparison of molecular electrostatic potential (MEP) distributions. It includes several modules. Module MEPPLA supplies MEP values for the points of a grid defined on a plane which is specified by a set of three points. The results of this program can easily be converted into MEP maps using third-parties graphical software. Module MEPMIN allows to find automatically the MEP minima of a molecular system. It supplies the cartesian coordinates of these minima, their values, and all the geometrical relationships between them (distances, angles, and dihedral angles). Module MEPCOMP computes a similarity coefficient between the MEP distributions of two molecules and finds their relative position that maximizes the similarity. Module MEPCONF performs the same process as MEPCOMP, considering not only the relative position of both molecules but also a conformational degree of freedom of one of them. The most recently developed module, MEPPAR, is another modification of MEPCOMP in order to compute the MEP similarity between two molecules, but only taking into account a particular plane. The latter module is particularly useful to compare MEP distributions generated by π systems of aromatic rings. MEPSIM can use several wavefunction computation approaches to obtain MEP distributions. MEPSIM has a menu type interface to simplify the following tasks: creation of input files from output files of external programs (GAUSSIAN and AMPAC/MOPAC), setting the parameters for the current computation, and submitting jobs to the batch queues of the computer. MEPSIM has been coded in FORTRAN and its current version runs on VMS/VAX computers.

Automatic determination of MEP patterns of molecules and its application to caffeine metabolism inhibitors

Abstract Software has been developed to locate and determine accurately all the Molecular Electrostatic Potential (MEP) minima of a molecule and to plot the MEP maps corresponding to planes containing any three desired points (minima, atoms or dummy points). The minima description can be used as parameters in QSAR. Some of these techniques are used in the analysis of substances which inhibit caffeine metabolism and other similar, but inactive, compounds. The goal is to find electrostatic requirements associated with this inhibitory activity.

Quantitative comparison of molecular electrostatic potential distributions from several semiempirical and ab initio wave functions

A quantitative comparative analysis of molecular electrostatic potential (MEP) distributions generated from different wave functions was carried out. Wave functions were computed by using MNDO, AMl, STO‐3G, 3‐21G, 4‐31G, 6‐31G, 4‐31G*, 6‐31G*, and 6‐31G** methods. Ten different compounds, which include usual atoms and groups of biomolecules, such as hydroxyl, carbonyl, amine, amide, imine, double and triple bonds, and heteroaromatic rings, were studied. For each compound, MEP values in the points of a common 3‐D grid were computed; thereafter, the similarity between each pair of MEP distributions generated by different methods was assessed. Similarities were measured using the Spearman rank correlation coefficient. A similarity matrix was obtained for each compound. Similarity matrices were averaged and a hierarchical cluster analysis was carried out to classify the different quantum chemical methods. In the compounds studied, the main conclusion is the negligible difference between the pattern of MEP distributions generated from all split valence basis sets (with and without polarization functions).

Maximum electrostatic similarity between biomolecules optimizing both relative positions and conformations

Abstract Software was developed to find automatically the maximum electrostatic similarity between biomolecules by varying the relative positions and the conformations of one of them. This similarity is defined by means of the Spearman correlation coefficient computed over the molecular electrostatic potential (MEP) values at points of a volume around the molecules. Several tests are presented, including a comparison between 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) and benzylamine (BZA), two substrates of monoamine oxidase B (MAO-B). The proposed algorithm can be useful for molecular modelling and quantitative structure-activity relationship (QSAR) studies.

Complete or partial comparison of molecular electrostatic potential distributions? some tests with 5-HT ligands

Abstract Two different strategies for finding the relative positions of maximum similarity between molecular electrostatic potential (MEP) distributions and for measuring their similarities were applied to several indole derivatives which are ligands of 5-hydroxytryptamine receptors. The first strategy takes into account the whole MEP distribution and allows one to discriminate between two groups of compounds according to their biological activity. In the second approach the MEP comparison is restricted to one plane which is considered relevant to receptor recognition.