Michal H. Kolář

University of Chemistry and Technology | VSCHT · Department of Physical Chemistry (ÚFCH)

The ribosome is a macromolecular complex which is responsible for protein synthesis in all living cells according to their transcribed genetic information. Using X-ray crystallography and, more recently, cryo-electron microscopy (cryo-EM), the structure of the ribosome was resolved at atomic resolution in many functional and conformational states....

The effect of polar flattening on the stability of 32 halogen-bonded complexes was investigated by utilizing CCSD(T)/CBS, DFT and DFT-SAPT/CBS methods. It is shown that the value of polar flattening increases with the decreasing value of studied isodensity. For the complexes investigated, the polar flattening based on the isodensity of 0.001 a.u. r...

To contribute to the understanding of noncovalent binding of halogenated molecules with biological activity, electrostatic potential (ESP) maps of more than 2500 compounds were thoroughly analysed. A peculiar region of positive ESP, called the σ-hole, is a concept of central importance for halogen bonding. We aim to simplify the view on σ-holes and...

Until recently, the description of halogen bonding by standard molecular mechanics has been poor, owing to the lack of the so-called σ hole localized at the halogen. This region of positive electrostatic potential located on top of a halogen atom explains the counterintuitive attraction of halogenated compounds interacting with Lewis bases. In mole...

A novel approach in molecular docking was successfully used to reproduce protein-ligand experimental geometries. When dealing with halogenated compounds the correct description of halogen bonds between the ligand and the protein is shown to be essential. Applying a simple molecular mechanistic model for halogen bonds improved the protein-ligand geo...

The ribosome, owing to its exceptional conservation, harbours a remarkable molecular fossil known as the protoribosome. It surrounds the peptidyl transferase center (PTC), responsible for peptide bond formation. While previous studies have demonstrated the PTC activity in RNA alone, our investigation reveals the intricate roles of the ribosomal pro...

The ribosome, owing to its exceptional conservation and biological importance, harbours a remarkable molecular fossil known as the protoribosome. It surrounds the peptidyl transferase center (PTC), responsible for peptide bond formation. While previous studies have demonstrated the PTC activity in RNA alone, our investigation reveals the intricate...

Large biomolecular systems are at the heart of many essential cellular processes. The dynamics and energetics of an increasing number of these systems are being studied by computer simulations. Pushing the limits of length- and timescales that can be accessed by current hard- and software has expanded the ability to describe biomolecules at differe...

Proteosynthesis on ribosomes is regulated at many levels. Conformational changes of the ribosome, possibly induced by external factors, may transfer over large distances and contribute to the regulation. The molecular principles of this long-distance allostery within the ribosome remain poorly understood. Here, we use structural analysis and atomis...

Proteosynthesis on ribosomes is regulated at many levels. Conformational changes of the ribosome, possibly induced by external factors, may transfer over large distances and contribute to the regulation. The principles of this long-distance allostery within the ribosome remain poorly understood. Here, we use structural analysis and atomistic molecu...

Partial atomic charges belong to key concepts of computational chemistry. In some cases, however, they fail in describing the electrostatics of molecules. One such example is the σ‐hole, a region of positive electrostatic potential located on halogens and other atoms. In molecular mechanics, the σ‐hole is often modeled as a pseudo‐atom with a posit...

The ribosome is a fundamental biomolecular complex that synthesizes proteins in cells. Nascent proteins emerge from the ribosome through a tunnel, where they may interact with the tunnel walls or small molecules such as antibiotics. These interactions can cause translational arrest with notable physiological consequences. Here, we studied the arres...

Partial atomic charges belong to key concepts of computational chemistry. In some cases, however, they fail in describing the electrostatics of molecules. One such example is the $\sigma$-hole, a region of positive electrostatic potential located on halogens and other atoms. In molecular mechanics, the $\sigma$-hole is often modeled as a pseudo-ato...

The ribosome is a fundamental biomolecular complex responsible for protein production in cells. Nascent proteins emerge from the ribosome through a tunnel, where they may interact with the tunnel walls or small molecules such as antibiotics. These interactions can cause translational arrest with notable physiologic consequences. Here, we studied th...

The proteasome is a large biomolecular complex responsible for protein degradation. It is under intense research due to its fundamental role in cellular homeostasis, and tremendous potential for medicinal applications. Recent data from X-ray crystallography and cryo-electron microscopy have suggested that there is a large-scale structural change up...

Halogen bond (X‐bond) is a noncovalent interaction between a halogen atom and an electron donor. It is often rationalized by a region of the positive electrostatic potential on the halogen atom, so‐called σ‐hole. The X‐bond strength increases with the atomic number of the halogen involved; thus, for heavier halogens, relativistic effects become of...

Targeting energy metabolism in Mycobacterium tuberculosis (Mtb) is a new paradigm in the search for innovative anti-TB drugs. NADH:menaquinone oxidoreductase is a non-proton translocating type II NADH dehydrogenase (NDH-2) that is an essential enzyme in the respiratory chain of Mtb and is not found in mammalian mitochondria. Phenothiazines (PTZs) r...

Halogen bond (X-bond) is a noncovalent interaction between a halogen atom and an electron donor. It is often rationalized by a region of the positive electrostatic potential on the halogen atom, so-called $\sigma$-hole. The X-bond strength increases with the atomic number of the halogen involved, thus for heavier halogens, relativistic effects beco...

Halogen bonding (X-bonding) has attracted notable attention among noncovalent interactions. This highly directional attraction between a halogen atom and an electron donor has been exploited in knowledge-based drug design. A great deal of information has been gathered about X-bonds in protein-ligand complexes, as opposed to nucleic acid complexes....

A polarizable environment, prominently the solvent, responds to electronic changes in biomolecules rapidly. The knowledge of conformational relaxation of the biomolecule itself, however, may be scarce or missing. In this work, we describe in detail the structural changes in DNA undergoing electron transfer between two adjacent nucleobases. We emplo...

In the field of noncovalent interactions a new paradigm has recently become popular. It stems from the analysis of molecular electrostatic potentials and introduces a label, which has recently attracted enormous attention. The label is σ-hole, and it was first used in connection with halogens. It initiated a renaissance of interest in halogenated c...

Correction for 'The strength and directionality of a halogen bond are co-determined by the magnitude and size of the σ-hole' by Michal Kolář et al., Phys. Chem. Chem. Phys., 2014, 16, 9987–9996.

Human aldo-keto reductase 1B15 (AKR1B15) is a newly discovered enzyme which shares 92% amino acid sequence identity with AKR1B10. While AKR1B10 is a well characterized enzyme with high retinaldehyde reductase activity, involved in the development of several cancer types, the enzymatic activity and physiological role of AKR1B15 are still poorly know...

The effect of halogen-to-hydrogen bond substitution on the binding energetics and biological activity of an aldose reductase inhibitor has been studied using X-ray crystallography, IC50 measurements, advanced binding free energy calculations and simulations. The replacement of Br or I atoms by an amine (NH2) group has not induced changes in the ori...

The nature of halogen bonding in 128 complexes was investigated using advanced quantum mechanical calculations. First, isolated halogen donors were studied and their σ-holes were described in terms of size and magnitude. Later, both partners in the complex were considered and their interaction was described in terms of DFT-SAPT decomposition. The w...

The σ-holes of halogen atoms on various aromatic scaffolds were described in terms of their size and magnitude. The electrostatic potential maps at the CAM-B3LYP-D3(bj)/def2-QZVP level were calculated and the σ-holes of more than 100 aromatic analogues were thoroughly analysed to relate the σ-holes to the binding preferences of the halogenated comp...

This Minireview discusses the latest developments in modern quantum mechanics (QM)-based computer-aided drug design, especially using semiempirical QM (SQM) methods. It first tackles biochemical and biophysical quantities and the approaches to their measurements. Protein–ligand affinities are determined mostly by noncovalent interactions. The text...

In this paper, we studied a designed series of aldose reductase (AR) inhibitors. The series had been derived from a known AR binder which had previously been shown to form a halogen bond between its bromine atom and the oxygen atom of the Thr-113 side chain of AR. In the series, the strength of the halogen bond was modulated by two factors, namely...

The crystals of benzene and hexahalogenbenzenes have been studied by means of the density-functional theory augmented by an empirical dispersion correction term as well as by the symmetry-adapted perturbation theory. In order to elucidate the nature of noncovalent binding, pairwise interactions have been investigated. It has been demonstrated that...

The accuracy and performance of implicit solvent methods for solvation free energy calculations were assessed on a set of 20 neutral drug molecules. Molecular dynamics (MD) provided ensembles of conformations in water and water-saturated octanol. The solvation free energies were calculated by popular implicit solvent models based on quantum mechani...

Various cluster models of graphene and a periodic graphene with two organic electron acceptors (tetracyanoethylene and tetracyanoquinodimethane) were investigated by means of several quantum chemical and molecular mechanical approaches. The benchmark interaction energies of the coronene complexes were calculated at the MP2.5/CBS/6-31G*(0.25) level...

A DNA dodecamer and the methyladenine···methylthymine (mA···mT) complex in aqueous environment have been studied by means of molecular dynamics simulation, with a modified force field accounting for the hypothetical absence of London dispersion forces. Under these conditions, the mA···mT complex is preserved, while the double-helical DNA oligomer p...

In this study, an extensive sampling of the conformational space of nine HIV-1 protease inhibitors was performed to estimate the uncertainty with which a single-conformation scoring scheme approximates the ligand-protein binding free energy. The SMD implicit solvation/desolvation energy and gas-phase PM6-DH2 energy were calculated for a set of 1600...

We investigated the intercalation of an antitumor drug ellipticine into four adenine-thymine (AT) rich DNA duplexes with the focus on the configurational entropy, by means of molecular dynamics (MD) simulations. Two possible binding orientations of ellipticine in a DNA double helix were studied, and the orientation with the pyrrole nitrogen exposed...

The reliability of the AMBER force field is tested by comparing the total interaction energy and dispersion energy with the reference data obtained at the density functional theory-symmetry-adapted perturbation treatment (DFT-SAPT)/aug-cc-pVDZ level. The comparison is made for 194 different geometries of noncovalent complexes (H-bonded, stacked, mi...

The structure of the phenol dimer and phenol...methanol complexes was determined by gradient optimization using the Hartree-Fock (HF), MP2, DFT, and RI-DFT-D methods with various basis sets. Theoretical rotational constants were compared with experimental values and the following conclusions were made: (1) HF and DFT methods fail to predict cluster...