Jan Rezac

Jan Rezac
Institute of Organic Chemistry and Biochemistry of the CAS · Department of Computational Chemistry

Doc. PhD

About

126
Publications
16,760
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Introduction
I am computational chemist interested mainly in non-covalent interactions. My projects range from accurate calculations of model systems and development of data sets of benchmark interaction energies (such as the S66, X40 and A24 sets) to development of semiempirical QM methods able to describe non-covalent interactions. I am also developing an open-source software framework CUBY that allows integration of various calculations and automation of complex computational workflows.
Additional affiliations
November 2013 - present
Palacký University Olomouc
Position
  • Professor (Associate)
September 2009 - present
Institute of Organic Chemistry and Biochemistry of the CAS
Position
  • Researcher
September 2009 - October 2013
Palacký University Olomouc
Position
  • Lecturer

Publications

Publications (126)
Chapter
In this chapter, we will see how fast quantum mechanical (QM) calculations can be performed for molecules with semiempirical QM methods. The latter can be derived from the wavefunction-based (discussed in Chapter 1) or density-functional theory (discussed in Chapter 2) frameworks by introducing rather drastic approximations, and then fitting parame...
Article
The SH250×10 dataset presented here extends the Non-Covalent Interactions Atlas database (https://www.nciatlas.org) to complexes bound by σ-hole interactions - halogen, chalcogen and pnictogen bonds. It comprises 250 complexes where Cl, Br, I, S, Se, P and As interact with diverse electron donors. An accurate CCSD(T)/CBS benchmark is provided for t...
Preprint
The SH250×10 dataset presented here extends the Non-Covalent Interactions Atlas database (www.nciatlas.org) to complexes bound by σ-hole interactions – halogen, chalcogen and pnictogen bonds. It comprises 250 complexes where Cl, Br, I, S, Se, P and As interact with diverse electron donors. An accurate CCSD(T)/CBS benchmark is provided for ten point...
Article
Second-order Møller-Plesset perturbation theory (MP2) provides a valuable alternative to density functional theory for modeling problems in organic and biological chemistry. However, MP2 suffers from known limitations in the description of van der Waals (London) dispersion interactions and reaction thermochemistry. Here, a spin-component-scaled, di...
Preprint
Full-text available
The Non-Covalent Interactions Atlas (www.nciatlas.org) has been extended with two data sets of benchmark interaction energies in complexes dominated by London dispersion. The D1200 data set of equilibrium geometries provides a thorough sampling of an extended chemical space, while the D442×10 set features dissociation curves for selected complexes....
Preprint
Full-text available
Second-order Møller-Plesset perturbation theory (MP2) provides a valuable alternative to density functional theory for modeing problems in organic and biological chemistry. However, MP2 suffers from known lim- itations in the description of van der Waals dispersion interactions and reaction thermochemistry. Here, a spin-component-scaled, dispersion...
Preprint
Second-order Møller-Plesset perturbation theory (MP2) provides a valuable alternative to density functional theory for modeing problems in organic and biological chemistry. However, MP2 suffers from known lim- itations in the description of van der Waals dispersion interactions and reaction thermochemistry. Here, a spin-component-scaled, dispersion...
Article
Full-text available
Performance of computational methods in modelling cyclic dinucleotides-an important and challenging class of compounds-has been evaluated by two different benchmarks: (1) gas-phase conformational energies and (2) qualitative agreement with NMR observations of the orientation of the w-dihedral angle in solvent. In gas-phase benchmarks, where CCSD(T)...
Article
The new R739×5 data set from the Non-Covalent Interactions Atlas series (www.nciatlas.org) focuses on repulsive contacts in molecular complexes, covering organic molecules, sulfur, phosphorus, halogens, and noble gases. Information on the repulsive parts of the potential energy surface is crucial for the development of robust empirically parametriz...
Preprint
The new R739×5 data set from the Non-Covalent Interactions Atlas series (www.nciatlas.org) focuses on repulsive contacts in molecular complexes, covering organic molecules, sulfur, phosphorus, halogens and noble gases. Information on the repulsive parts of the potential energy surface is crucial for the development of robust empirically parametrize...
Article
Full-text available
The success of approximate computational methods, such as molecular mechanics, or dispersion-corrected density functional theory, in the description of non-covalent interactions relies on accurate parameterizations. Benchmark data sets are thus required. This area is well developed for organic molecules and biomolecules but practically non-existent...
Article
Invited for this month's cover is the group of Prof. Pavel Hobza, Czech Academy of Sciences, Prague. The cover picture shows a powerful automated quantum mechanics based SQM/COSMO approach to protein–ligand scoring. It comprises thorough preparation of ligand structures, extensive generation of binding complexes, fast geometry relaxation and reliab...
Cover Page
Full-text available
The Front Cover shows a powerful automated quantum mechanics based SQM/COSMO approach to protein–ligand scoring. It comprises thorough preparation of ligand structures, extensive generation of binding complexes, fast geometry relaxation, and reliable affinity prediction. SQM/COSMO outperforms standard tools in native pose recognition, affinity rank...
Preprint
The Non-Covalent Interactions Atlas (www.nciatlas.org) aims to provide a new generation of benchmark data sets for non-covalent interactions. The HB300SPX data set presented here extends the coverage of hydrogen bonds to phosphorus, sulfur and halogens up to iodine. It is again complemented by a set of dissociation curves, HB300SPX×10. The new data...
Article
Quantum mechanical (QM) methods have been gaining importance in structure‐based drug design where a reliable description of protein‐ligand interactions is of utmost significance. However, strategies i.e. QM/MM, fragmentation or semiempirical (SQM) methods had to be pursued to overcome the unfavourable scaling of QM methods. Various SQM‐based approa...
Article
Full-text available
DFTB+ is a versatile community developed open source software package offering fast and efficient methods for carrying out atomistic quantum mechanical simulations. By implementing various methods approximating density functional theory (DFT), such as the density functional based tight binding (DFTB) and the extended tight binding method, it enable...
Article
The Non-Covalent Interactions Atlas project (www.nciatlas.org) aims to cover a wide range of noncovalent interactions with a new generation of benchmark data sets. This Article presents the first two data sets focused on hydrogen bonding: HB375, featuring neutral systems, and IHB100 for ionic H-bonds. Both data sets are complemented by 10-point dis...
Article
Full-text available
The semiempirical quantum mechanical (SQM) methods used in drug design are commonly parametrized and tested on data sets of systems that may not be representative models for drug–biomolecule interactions in terms of both size and chemical composition. This is addressed here with a new benchmark data set, PLF547, derived from protein–ligand complexe...
Preprint
The Non-Covalent Interactions Atlas project (www.nciatlas.org) aims to cover a wide range of non-covalent interactions with a new generation of benchmark data sets. This paper presents the first two data sets focused on hydrogen bonding: HB375, featuring neutral systems, and IHB100 for ionic H-bonds. Both data sets are complemented by ten-point dis...
Cover Page
Full-text available
The Front Cover shows the ability of SQM‐based frame to separate the actives (background: green spheres) from inactives (red spheres) while maintaining a powerful sampling (front: HSP90 crystal complex). More information can be found in the Article by S. M. Eyrilmez, C. Köprülüoğlu et al.
Cover Page
Full-text available
The image shows the ability of SQM‐based frame to separate the actives (background: green spheres) from inactives (red spheres) while maintaining a powerful sampling (front: HSP90 crystal complex). Read the full text of the Article at 10.1002/cphc.201900628. “The performance of a newly developed scoring function (SF), based on the semiempirical QM...
Article
This paper describes the excellent performance of a newly developed scoring function (SF), based on the semiempirical QM (SQM) PM6‐D3H4X method combined with the conductor‐like screening implicit solvent model (COSMO). The SQM/COSMO, Amber/GB and nine widely used SFs have been evaluated in terms of ranking power on the HSP90 protein with 72 biologi...
Article
This article analyzes the ability of semiempirical quantum‐mechanical methods (PM6 and PM7) and self‐consistent charge density‐functional tight‐binding (SCC‐DFTB) method DFTB3 to describe halogen bonds. Calculations of the electrostatic potential on the surface of molecules containing halogens show that the σ‐hole could be described well in modifie...
Article
An accurate description of solvation effects is of high importance in modeling biomolecular systems. Our main interest is to find an accurate yet efficient solvation model for semiempirical quantum-mechanical methods applicable to large protein-ligand complexes in the context of computer-aided drug design. We present a survey of readily available m...
Article
Full-text available
Functionality of enzymes is strongly related to water dynamic processes. The control of the redox potential for metallo-enzymes is intimately linked to the mediation of water molecules in the first...
Article
Non-covalent interactions govern many important areas of chemistry ranging from biomolecules to molecular crystals. Here, an accurate and computationally inexpensive dispersion-corrected second-order Moller-Plesset perturbation theory model (MP2D) is presented. MP2D recasts the highly successful dispersion-corrected MP2C model in a framework based...
Chapter
This chapter reviews the current status of structure‐based computer‐aided drug design of boron cluster‐containing protein ligands. In computer‐aided structure‐based drug design, the ligand's binding pose within the protein is predicted by docking, a task that has practically been mastered for the broad organic chemistry space. Scoring is thereafter...
Data
This file contains Heat map of RMSE in kcal/mol for different SQM methods tested over R160×6 benchmark data set; element pairwise parameters optimized over R160×6 and S66×8 benchmark data sets respectively for SCCDFTB and PM6 methods; list of benchmark energies for the 960 complexes corresponding to different element pair contacts.
Article
Full-text available
Semiempirical QM methods with corrections for non-covalent interactions provide a favorable combination of accuracy and computational efficiency what makes them useful tool for a study of large molecular systems. It was, however, noted that the accuracy of these method deteriorates at intermolecular distances shorter than equilibrium. In this work,...
Article
Carefully selected set of acyclic and cyclic model peptides and several other macrocycles comprising 13 compounds in total, has been used to calibrate accuracy of DFT(-D3) method for conformational energies, employing BP86, PBE0, PBE, B3LYP, BLYP, TPSS, TPSSh, M06-2X, B97-D, OLYP, revPBE, M06-L, SCAN, revTPSS, BH-LYP, and ωB97X-D3 functionals. Both...
Article
Model: 2014, 54, 2680), three represent potential macrocyclic inhibitors of human cyclophilin A. The free energy values (GDFT/COSMO-RS) for all conformers of each compound were obtained by the composite protocol based on the in vacuo quantum mechanics (DFT-D3 method in a large basis set), standard gas-phase thermodynamics and the COSMO-RS solvatio...
Article
This paper presents a study of pnictogen bonding in a series of pyrazine•PnX5 (Pn = P, As, Sb and X = F, Cl, Br) complexes. The whole series was studied computationally. Moreover, the pyrazine complexes with PCl5 and SbCl5 were prepared and characterized experimentally. It was found that the Pn-N distances are only slightly elongated when compared...
Article
The description of hydrogen bonds in the density-functional tight-binding (DFTB) method continues to be a challenging task because the approximations that make the method computationally efficient compromise already the first-order electrostatic contribution to the interaction. So far, the best results have been achieved with fully empirical correc...
Article
Full-text available
The noncovalent interactions are ubiquitous and represent a very important binding motif. The direct experimental measurement of binding energies in complexes has been elusive for a long time despite its importance, for instance, for understanding and predicting the structure of bio-macromolecules. Here we report a combined experimental and computa...
Article
Full-text available
General and reliable description of structures and energetics in protein–ligand (PL) binding using the docking/scoring methodology has until now been elusive. We address this urgent deficiency of scoring functions (SFs) by the systematic development of corrected semiempirical quantum mechanical (SQM) methods, which correctly describe all types of n...
Article
Calculations of interaction energies of noncovalent interactions in small basis sets are affected by the basis set superposition error and dispersion-corrected DFT-D methods are thus usually parameterised only for triple-zeta and larger basis sets. Nevertheless, some smaller basis sets could also perform well. Among many combinations tested, we obt...
Article
Full-text available
Close B−H···π contacts have recently been observed in crystallographic structures of Ir-dithiolene-phosphine complexes containing boron hydride cluster. This finding was interpreted using quantum chemical calculations as a new type of electrostatically driven nonclassical hydrogen bonding. However, such an explanation contradicts the wealth of evid...
Article
In DFT-SAPT interaction energy calculations, the most demanding step is the calculation of the London dispersion term. To avoid this bottleneck and make DFT-SAPT applicable to larger systems, the ab initio dispersion terms can be replaced by one calculated empirically at an almost negligible cost (J. Phys. Chem. A 2011, 115, 11321–11330). We presen...
Article
Full-text available
We have analyzed the description of non-covalent interactions in multiple variants of the self-consistent charges density functional tight binding (SCC-DFTB) method. While the description of London dispersion can be easily improved by empirical correction, hydrogen bonding poses a much more difficult problem. We have implemented an interaction ener...
Article
To increase fidelity of docking/scoring to identify native protein-ligand poses, we have recently introduced the “SQM/COSMO” scoring function which combines semi-empirical quantum mechanical description of noncovalent interactions at the PM6-D3H4X level and COSMO implicit model of solvation. This approach outperformed standard scoring functions but...
Article
Full-text available
The role of charge transfer in halogen bonding is the subject of an ongoing debate and controversy. It is clear from experimental data that charge transfer occurs in halogen bonds, but its contribution to the energetics of the interaction can be evaluated only computationally. Since the charge transfer is not a physically well-defined property, the...
Article
A training set of eleven X-ray structures determined for biomimetic complexes between cucurbit[n]uril (CB[7 or 8]) hosts and adamantane-/diamantane ammonium/aminium guests were studied with DFT-D3 quantum mechanical computational methods to afford ΔGcalcd binding energies. A novel feature of this work is that the fidelity of the BLYP-D3/def2-TZVPP...
Article
Halogen bonds are a subset of noncovalent interactions with rapidly expanding applications in materials and medicinal chemistry. While halogen bonding is well known in organic compounds, it is new in the field of boron cluster chemistry. We havesynthesized and crystallized carboranes containing Br atoms in two different positions, namely bound to C...
Article
The strength and nature of the connection in Lappert's stannylene dimer ({Sn[CH(SiMe3)2]2}2) and its smaller analogs, simplified stannylenes, as well as similar Ge complexes were studied by means of DFT-D3 calculations, energy decomposition analysis (EDA), electrostatic potential (ESP) and natural population analysis. The trans-bent structure of th...
Article
Data sets of benchmark interaction energies in noncovalent complexes are an important tool for quantifying the accuracy of computational methods used in this field, as well as for the development of new computational approaches. This review is intended as a guide to conscious use of these data sets. We discuss their construction and accuracy, list...
Article
Cuby is a computational chemistry framework written in the Ruby programming language. It provides unified access to a wide range of computational methods by interfacing external software and it implements various protocols that operate on their results. Using structured input files, elementary calculations can be combined into complex workflows. Fo...
Article
Full-text available
Noncovalent complexes of hydrophobic peptides GLLLG and GLLLK with photoleucine (L*) tagged peptides G(L*n Lm )K (n = 1,3, m = 2,0) were generated as singly charged ions in the gas phase and probed by photodissociation at 355 nm. Carbene intermediates produced by photodissociative loss of N2 from the L* diazirine rings underwent insertion into X−H...
Research
VIII congress of the International Society of Theoretical Chemical Physics” held at ISTCP, Budapest, Hungary, 25-31st August 2013.
Article
Current virtual screening tools are fast, but reliable scoring is elusive. Here, we present the ‘SQM/COSMO filter’, a novel scoring function featuring quantitative semiempirical quantum mechanical (SQM) description of all types of noncovalent interactions coupled with implicit COSMO solvation. We show unequivocally that it outperforms eight widely...
Conference Paper
Understanding the role of solvent in the binding of small-molecule ligands to protein active sites is a key objective of computational drug design. It has been shown that displacement of high-energy water molecules from a protein active site by the ligand is a principal source of the binding free energy. Here we present a computational analysis of...
Article
Many-body noncovalent interactions are increasingly important in large and/or condensed-phase systems, but the current understanding of how well various models predict these interactions is limited. Here, benchmark complete-basis set coupled cluster singles, doubles, and perturbative triples (CCSD(T)) calculations have been performed to generate a...
Article
Full-text available
The A24 data set (Řezáč and Hobza, J. Chem. Theory Comput. 2013, 9, 2151-2155) is a set of noncovalent complexes large enough to showcase various types of interactions yet small enough to make highly accurate calculations possible. It is intended for the testing of accurate computational methods which are then used as a benchmark in larger model sy...
Article
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...
Article
We present a concerted experimental and theoretical study of the anisoleArn complexes with n = 1-3. Experimentally, anisole was seeded into a pulsed supersonic argon jet producing a molecular beam. Resonant two-photon, two-colour ionisation (R2PI) spectra of anisoleArn complexes with n = 1-3 were obtained. Also, the photodissociation of the (1 : 1)...
Article
Among noncovalent interactions, π-π stacking is a very important binding motif governed mainly by London dispersion. Despite its importance, for instance, for the structure of bio-macromolecules, the direct experimental measurement of binding energies in π-π stacked complexes has been elusive for a long time. Only recently, an experimental value fo...
Article
Full-text available
The density functional code deMon2k employs a fitted density throughout (Auxiliary Density Functional Theory), which offers a great speed advantage without sacrificing necessary accuracy. Powerful Quantum Mechanical/Molecular Mechanical (QM/MM) approaches are reviewed. Following an overview of the basic features of deMon2k that make it efficient wh...
Article
Separation of the energetic contribution of charge transfer to interaction energy in noncovalent complexes would provide important insight into the mechanisms of the interaction. However, the calculation of charge-transfer energy is not an easy task. It is not a physically well-defined term, and the results might depend on how it is described in pr...
Article
We present an extension to the recent 3OB parametrization of the Density Functional Tight Binding Model DFTB3 for biological and organic systems. Parameters for the halogens F, Cl, Br, and I have been developed for use in covalently bound systems and benchmarked on a test set of 106 molecules (the ‘OrgX’ set), using bonding distances, bonding angle...
Conference Paper
Reliable scoring of docking poses is the Holy Grail for the academic and industrial pharmaceutical research. It is well known that different docking/scoring approaches give different ranking of poses. The scores are obtained via statistical, empirical or physics-based functions. In the last category, we have undertaken a broad and careful developme...
Article
Hydrogen fluoride dimer is a perfect model system for studying hydrogen bonding. Its size makes it possible to apply the most advanced theoretical methods available, yet it is a full-featured complex of molecules with nontrivial electronic structure and dynamic properties. Moreover, the dissociation energy of the HF dimer has been measured experime...
Article
Full-text available
Recently, it has become possible to apply higher-order coupled-cluster methods to polyatomic systems including molecular noncovalent complexes. Due to the steep scaling of the complexity of these calculations, the size of the basis set becomes a critical factor and larger systems can be calculated only in small basis sets. To obtain the most accura...
Article
Two novel carborane-sulfamide inhibitors of human carbonic anhydrase II (hCAII) have been studied using QM/MM calculations. The neutral closo-carborane cage was bound to hCAII mainly via dispersion interactions and formed only very weak dihydrogen bonds. On the contrary, the monoanionic nido cage interacted with the protein mainly via electrostatic...
Article
Full-text available
In Nature, the family of copper monooxygenases comprised of peptidylglycine α-hydroxylating monooxygenase (PHM), dopamine β-monooxygenase (DβM), and tyramine β-monooxygenase (TβM) is known to perform dioxygen-dependent hydroxylation of aliphatic CH bonds by using two uncoupled metal sites. In spite of many investigations, including biochemical, ch...
Article
The quantum mechanics (QM)-based scoring function that we previously developed for the description of noncovalent binding in protein-ligand complexes has been modified and extended to treat covalent binding of inhibitory ligands. The enhancements are: (i) the description of the covalent-bond breakage/formation using hybrid QM/semiempirical QM (QM/S...
Article
We present a novel parallel gradient optimization algorithm designed for the optimization of molecular geometry - the parallel preconditioned LBFGS (PP-LBFGS) method. In each step, several additional gradient calculations (performed in parallel with the calculation of the potential) are used to improve the most important elements of the Hessian. Th...
Article
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...
Article
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...