Biomedical subjects

Xavier Gironés

Publications and source records attributed to Xavier Gironés.

10 recordsLinked to original sources

PubMed2004

TGSA-Flex: Extending the capabilities of the Topo-Geometrical Superposition Algorithm to handle flexible molecules.

In this work, an extension of the already studied Topo-Geometrical Superposition Approach (TGSA) is presented. TGSA, a general-purpose, fast, automatic, and user-intuitive three-dimensional molecular alignment procedure, was originally designed to superpose rigid molecules simply based on atomic numbers, molecular coordinates, and connectivity. The algorithm is further developed to enable handling rotations around single bonds; in this way, common structural features, which were not properly aligned due to conformational causes, can be brought together, thus improving the molecular similarity picture of the final alignment. The present procedure, implemented in Fortran 90 and named TGSA-Flex, is deeply detailed and tested over four molecular sets: amino acids, nordihydroguaiaretic acid (NDGA) derivatives, HIV-1 protease inhibitors, and 1-[2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) derivatives. TGSA-Flex performance is evaluated by means of computational time, number of superposed atoms (also comparing it with respect to the rigid approach), and index of fit between the compared structures.

Amino Acids↗

PubMed2003

Rational modelling of the voltage-dependent K+ channel inactivation by aminopyridines.

A functional model for the in vitro inactivation of voltage-dependent K(+) channels is developed. The model expresses the activity as a function of the aminopyridine pK(a), the interaction energy with the receptor, and a quotient of partition functions. Molecular quantum similarity theory is introduced in the model to express the activity as a function of the principal components of the similarity matrix for a series of agonists. To validate the model, a set of five active (protonated) aminopyridines is considered: 2-aminopyridine, 3-aminopyridine, 4-aminoquinoleine, 4-aminopyridine, and 3,4-diaminopyridine. A regression analysis of the model gives good results for the variation of the observed activity with the overlap similarity index when pyridinic rings are superposed. The results support the validity of the model, and the hypothesis of a ligand-receptor entropy variation depending mainly on the nature of the ligand. In addition, the results suggest that the pyridinic ring must play an active role in the interaction with the receptor site. This interaction with the protonated pyridinic nitrogen can involve a cation-pi interaction or a donor hydrogen bond. The amine groups, at different relative positions of the pyridinic nitrogen, can form one or more hydrogen bonds due to the C(4) symmetry of the inner part of the pore in the K(+) channel.

Aminopyridines↗

PubMed2002

Molecular quantum similarity and the fundamentals of QSAR.

A general overview on quantum similarity and applications to QSAR is presented. The concepts regarding quantum similarity from its theoretical foundation and consecutive development, involving mathematical formulation and similarity measures, are presented and complemented with application examples. The practical part, based on the well-known Crammer 31 steroids set, covers approximate quantum similarity calculations, molecular superposition, and statistics. In this way, the reader will find both basic general information and applicability of quantum similarity.

Animals↗

PubMedDate not supplied

Using molecular quantum similarity measures under stochastic transformation to describe physical properties of molecular systems.

The application of molecular quantum similarity measures (MQSM) to correlate physicochemical properties is reported. Satisfactory quantitative structure-property relationship (QSPR) models are obtained for three molecular sets, where boiling points and chromatographic retention times and indices are studied. In this work, MQSM are scaled using a stochastic transformation and related to molecular properties using the partial least-squares technique.

Journal Article↗

PubMedDate not supplied

Modeling large macromolecular structures using promolecular densities.

A procedure to easily construct fitted density functions is presented. This methodology, based on the promolecule approach, is able to handle large macromolecular systems, such as proteins. The usual procedure dealing with fitted densities has been improved by adding some restrictions, which allow faster calculations. As a main application example, molecular isodensity contours (MIDCOs) are constructed for two proteins, one of them composed of more than 50 000 atoms. MIDCOs, as a visual representation of the molecular density function, and thus an important descriptor of the molecular charge distribution, constitute a powerful tool in the understanding of molecular systems. MIDCOs are presented for both proteins, allowing exploration of their surfaces, as well as analysis of their shapes. Also, as a quantum mechanical calculation example, molecular quantum self-similarity measures are calculated for several proteins.

Computer Simulation↗

PubMedDate not supplied

Molecular basis of LFER. Modeling of the electronic substituent effect using fragment quantum self-similarity measures.

A new approach allowing the theoretical modeling of the electronic substituent effect is proposed. The approach is based on the use of fragment Quantum Self-Similarity Measures (MQS-SM) calculated from domain averaged Fermi Holes as new theoretical descriptors allowing for the replacement of Hammett sigma constants in QSAR models. To demonstrate the applicability of this new approach its formalism was applied to the description of the substituent effect on the dissociation of a broad series of meta and para substituted benzoic acids. The accuracy and the predicting power of this new approach was tested on the comparison with a recent exhaustive study by Sullivan et al. It has been shown that the accuracy and the predicting power of both procedures is comparable, but, in contrast to a five-parameter correlation equation necessary to describe the data in the study, our approach is more simple and, in fact, only a simple one-parameter correlation equation is required.

Journal Article↗

PubMedDate not supplied

Molecular quantum similarity-based QSARs for binding affinities of several steroid sets.

The application of Molecular Quantum Similarity Measures (MQSM) to correlate biological activities for three different sets of steroids is reported. A general protocol for the generation of descriptors is detailed, thus covering molecular superposition, electronic density fitting, and quantum similarity calculation issues. Satisfactory Quantitative Structure-Activity Relationship (QSAR) models (r(2) in [0.69,0.94] and q(2) in [0.59,0.73]), comparable to previous studies, are obtained in all cases, where steroid binding affinities to different enzymes are studied. In this work, MQSM, properly scaled using Carbó Index, are related to activity using a Partial Least Squares routine.

Aromatase↗

PubMedDate not supplied

Quantum similarity superposition algorithm (QSSA): a consistent scheme for molecular alignment and molecular similarity based on quantum chemistry.

The use of the molecular quantum similarity overlap measure for molecular alignment is investigated. A new algorithm is presented, the quantum similarity superposition algorithm (QSSA), expressing the relative positions of two molecules in terms of mutual translation in three Cartesian directions and three Euler angles. The quantum similarity overlap is then used to optimize the mutual positions of the molecules. A comparison is made with TGSA, a topogeometrical approach, and the influence of differences on molecular clustering is discussed.

Aldosterone↗

PubMedDate not supplied

Topological quantum similarity indices based on fitted densities: theoretical background and QSPR application.

A novel methodology to derive adjacency matrices for 3-dimensional molecules is presented in this work. These matrices, which are derived from atomic quantum similarity calculations, allow redefining several adjacency matrix-based topological indices, such as Randić, Zagreb or Chi's. The present derivation is built upon a previous work, where a simpler class of density function was used to describe the atoms composing the molecule, and the present proposal suggests using fitted atomic densities from the Atomic Shell Approximation procedure, which has been proved to appropriately reproduce, in its application space, atomic ab initio densities. The construction of such matrices as well as the derived indices are presented, along with some QSPR, where these topological indices are used as molecular descriptors for heat of formation, inhibition, and toxicity with promising results.

Journal Article↗

PubMedDate not supplied

Molecular Quantum Similarity Measures from Fermi hole densities: modeling Hammett sigma constants.

A new approach, based on the use of fragment Quantum Self-Similarity Measures (MQS-SM) as descriptors of electronic substituent effect in aromatic series, was proposed. The novelty of this approach consists of the fact that the corresponding MQS-SM are not derived, as usual, from ordinary density functions (DF) but from the so-called domain averaged Fermi holes. This approach was applied to the study of substituent effects on the acidobasic dissociation constants in 6 series of para-substituted aromatic carboxylic acids. It has been shown that MQS-SM calculated for each particular set of acids correlate with the Hammett substituent constants. As a consequence, the corresponding similarity measures can be used as new efficient descriptors of the substituent effect, which hopefully could replace empirical sigma constants in QSAR models.

Models, Theoretical↗