Semiempirical calculations of binding enthalpy for protein–ligand complexes

Nikitina, E. A.; Сулимов, В. Б.; Zayets, Valentin A.; Зайцева, Наталья Владимировна

doi:10.1002/qua.10778

Cited by 70 publications

(70 citation statements)

References 46 publications

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“…Specifically, interactions are considered between a proton donor (including weak proton donors) and a conjugated system, between cations of various sorts and a conjugated system and between different conjugated systems (stacking and other types of interaction). The semiempirical PM3 method was used for calculations of enthalpy changes related to eight model systems for protein...ligand complexes 264 . Although good agreement was found between calculated and observed values, we are puzzled that this is the case when using a semiempirical procedure.…”

Section: Recognition At the Molecular Levelmentioning

confidence: 99%

The World of Non-Covalent Interactions: 2006

Hobza¹,

Zahradník²,

Müller‐Dethlefs³

2006

Collect. Czech. Chem. Commun.

247

235

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The review focusses on the fundamental importance of non-covalent interactions in nature by illustrating specific examples from chemistry, physics and the biosciences. Laser spectroscopic methods and both ab initio and molecular modelling procedures used for the study of non-covalent interactions in molecular clusters are briefly outlined. The role of structure and geometry, stabilization energy, potential and free energy surfaces for molecular clusters is extensively discussed in the light of the most advanced ab initio computational results for the CCSD(T) method, extrapolated to the CBS limit. The most important types of non-covalent complexes are classified and several small and medium size non-covalent systems, including H-bonded and improper H-bonded complexes, nucleic acid base pairs, and peptides and proteins are discussed with some detail. Finally, we evaluate the interpretation of experimental results in comparison with state of the art theoretical models: this is illustrated for phenol...Ar, the benzene dimer and nucleic acid base pairs. A review with 270 references.

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Section: Recognition At the Molecular Levelmentioning

confidence: 99%

The World of Non-Covalent Interactions: 2006

Hobza¹,

Zahradník²,

Müller‐Dethlefs³

2006

Collect. Czech. Chem. Commun.

247

235

View full text Add to dashboard Cite

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“…The affinity of a ligand for its receptor can also be evaluated by means of semiempirical QM methods,7–11 such as AM112 or PM3,13 which allow the physico‐chemical properties of medium‐sized and large systems to be investigated with a reasonable computational cost. In spite of the known limitations of semiempirical methods based on the neglect diatomic differential overlap (NDDO) approximation,14–16 they continue to find use in different applications such as the prediction of specific surface interactions on silica17 or carbon nanotubes,18 the qualitative interpretation of ligand‐protein19 interactions, and the estimation of the solvation contribution20 in those kinds of interactions. One of the problems associated with NDDO‐based methods is that they do not reproduce hydrogen bonding with good accuracy.…”

Section: Introductionmentioning

confidence: 99%

Are AM1 ligand‐protein binding enthalpies good enough for use in the rational design of new drugs?

et al. 2005

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We have examined the performance of semiempirical quantum mechanical methods in solving the problem of accurately predicting protein-ligand binding energies and geometries. Firstly, AM1 and PM3 geometries and binding enthalpies between small molecules that simulate typical ligand-protein interactions were compared with high level quantum mechanical techniques that include electronic correlation (e.g., MP2 or B3LYP). Species studied include alkanes, aromatic systems, molecules including groups with hypervalent sulfur or with donor or acceptor hydrogen bonding capability, as well as ammonium or carboxylate ions. B3LYP/6-311+G(2d,p) binding energies correlated very well with the BSSE corrected MP2/6-31G(d) values. AM1 binding enthalpies also showed good correlation with MP2 values, and their systematic deviation is acceptable when enthalpies are used for the comparison of interaction energies between ligands and a target. PM3 otherwise gave erratic energy differences in comparison to the B3LYP or MP2 approaches. As one would expect, the geometries of the binding complexes showed the known limitations of the semiempirical and DFT methods. AM1 calculations were subsequently applied to a test set consisting of "real" protein active site-ligand complexes. Preliminary results indicate that AM1 could be a valuable tool for the design of new drugs using proteins as templates. This approach also has a reasonable computational cost. The ligand-protein X-ray structures were reasonably reproduced by AM1 calculations and the corresponding AM1 binding enthalpies are in agreement with the results from the "small molecules" test set.

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“…At first this may seem impractical due to considerable computing times. However, it has been shown that complex optimization and the use of detailed parameters significantly improve results and modelling of interactions (Hostaš, Řezáč & Hobza, 2013;Nikitina, Sulimov, Zayets & Zaitseva, 2004;Ohno, Kamiya, Asakawa, Inoue & Sakurai, 2001). …”

Section: Ligand and Protein Preparationmentioning

confidence: 99%

Acoplamiento Molecular: Avances Recientes y Retos

2018

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Nota: Artículo recibido el 18 de octubre de 2017 y aceptado el 02 de mayo de 2018. ARTÍCULO DE REVISIÓN abstractAutomated molecular docking aims at predicting the possible interactions between two molecules. This method has proven useful in medicinal chemistry and drug discovery providing atomistic insights into molecular recognition. Over the last 20 years methods for molecular docking have been improved, yielding accurate results on pose prediction. Nonetheless, several aspects of molecular docking need revision due to changes in the paradigm of drug discovery. In the present article, we review the principles, techniques, and algorithms for docking with emphasis on protein-ligand docking for drug discovery. We also discuss current approaches to address major challenges of docking.Key Words: chemoinformatics, computer-aided drug design, drug discovery, structure-activity relationships. Acoplamiento Molecular: Avances Recientes y Retos resuMenEl acoplamiento molecular automatizado tiene como objetivo proponer un modelo de unión entre dos moléculas. Este método ha sido útil en química farmacéutica y en el descubrimiento de nuevos fármacos por medio del entendimiento de las fuerzas de interacción involucradas en el reconocimiento molecular. Durante los últimos 20 años se ha modificado extensamente la técnica de acoplamiento molecular dando resultados precisos en la predicción de los modos de unión. Sin embargo, hay algunas áreas que requieren ser mejoradas substancialmente. En este trabajo se revisan principios, técnicas y algoritmos usados en los programas computacionales del acoplamiento molecular con enfoque en la interacción proteína-ligando aplicado al descubrimiento de nuevos fármacos. También se discuten las estrategias dirigidas a solucionar los principales retos de esta técnica computacional.Palabras Clave: descubrimiento de nuevos fármacos, diseño de fármacos asistido por computadora, quimioinformática, relaciones estructura-actividad.

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Semiempirical calculations of binding enthalpy for protein–ligand complexes

Cited by 70 publications

References 46 publications

The World of Non-Covalent Interactions: 2006

The World of Non-Covalent Interactions: 2006

Are AM1 ligand‐protein binding enthalpies good enough for use in the rational design of new drugs?

Acoplamiento Molecular: Avances Recientes y Retos

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