Mikhail Darkhovskiy

• Master of Science
• Researcher at FreeCurve Labs

We model the auto-ionization of water by determining the free energy of hydration of the major intermediate species of water ions. We represent the smallest ions - the hydroxide ion OH- , the hydronium ion H3O+, and the Zundel ion H5O2+, - by bonded models; and the more extended ionic structures by strong non-bonded interactions (e.g. the Eigen H9O...

A key goal of molecular modeling is the accurate reproduction of the true quantum mechanical potential energy of arbitrary molecular ensembles with a tractable classical approximation. The challenges are that analytical expressions found in general purpose force fields struggle to faithfully represent the intermolecular quantum potential energy sur...

Protein-ligand binding free-energy calculations using molecular dynamics (MD) simulations have emerged as a powerful tool for in silico drug design. Here, we present results obtained with the ARROW force field (FF)─a multipolar polarizable and physics-based model with all parameters fitted entirely to high-level ab initio quantum mechanical (QM) ca...

The main goal of molecular simulation is to accurately predict experimental observables of molecular systems. Another long-standing goal is to devise models for arbitrary neutral organic molecules with little or no reliance on experimental data. While separately these goals have been met to various degrees, for an arbitrary system of molecules they...

The computation model for evaluation of conformational entropy changes upon binding ligands to receptors is described. Then, changes of conformational entropy component and of binding free energy are compared. Interest to conformational entropy arises from developing new drugs as it might be changed purposefully. It is shown that conformational ent...

The McWeeny's group functions technique is a natural way to introduce local description into quantum chemistry. It can also serve as a basis for constructing numerically effective computational schemes with almost linear scaling of computational costs with the size of a system. In this study, we apply it to the coordination compounds of Zn(II)-cont...

With use of cumulants of two-electron density matrices semiempirical and DFT methods are analyzed from a point of view of their suitability to describe qualitative features of electronic correlation important for molecular modelling of electronic structure of the transition metal complexes (TMC). It is shown that traditional semiempirical methods r...

With use of cumulants of two-electron density matrices semi-empirical and DFT methods are analyzed from a point of view of their suitability to describe qualitative features of electronic correlation impor-tant for molecular modeling of electronic structure of the transition metal complexes (TMC). It is shown that traditional semiempirical methods...

In contrast to antagonists, agonists tend to induce considerable conformational changes in their receptors, resulting in opening of ion channels, either directly or via secondary messengers. These conformational transformations require great energy expenses. However, the experimentally determined free energies of complexation between agonists and r...

With use of cumulants of two-electron density matrices semiempirical methods are analyzed from a point of view of their suitability to describe qualitative features of electronic correlation important for calculation of electronic structure of the transition metal complexes (TMC). It is shown that traditional semiempirical methods relying upon the...

The quantum mechanical effective Hamiltonian of crystal field (EHCF) methodology (previously developed for describing electronic structure of transition metal complexes) is combined with the Gillespie−Kepert version of molecular mechanics (MM) in order to describe multiple potential energy surfaces (PES) of the Werner-type complexes corresponding t...

A computational method targeted to Werner-type complexes is developed on the basis of quantum mechanical effective Hamiltonian crystal field (EHCF) methodology (previously proposed for describing electronic structure of transition metal complexes) combined with the Gillespie-Kepert version of molecular mechanics (MM). It is a special version of the...

When a drug molecule approaches a non-specific acceptor both molecules are in electrostatic fields of equal sign which prevents drug-acceptor complex formation. At the same time, the drug-acceptor system does not achieve the thermodynamic global minimum. Otherwise, when a certain drug interacts with its specific receptor, mutual compensation of the...

In the present work the semiempirical effective crystal field (ECF) method previously designed for electronic structure calculations of transition metal complexes and utilizing non-Hartree–Fock trial wave function and parameterized for complexes of doubly charged Cr2+, V2+, Mn2+, Fe2+, Co2+, and Ni2+ cations is extended to complexes of triply charg...

In the present work the semiempirical effective crystal field (ECF) method previously designed for electronic structure calculations of transition metal complexes and utilizing non-Hartree–Fock trial wave function and parameterized for complexes of doubly charged Cr2+, V2+, Mn2+, Fe2+, Co2+, and Ni2+ cations is extended to complexes of triply charg...

The effective crystal field (ECF) methodology previously developed for description of the electronic structure of transition metal complexes (TMCs) is combined with molecular mechanics (MM) formalism. In this way, a new method for calculations of potential energy surfaces of the Werner-type TMC is developed. It is based on a combined quantum mechan...

Experimental determination of the lifetimes of short-lived ligand – receptor complexes encounters considerable, frequently insurmountable difficulties because the conventional methods of “fast” kinetics widely used for the study of enzyme – substrate complexes are practically inapplicable to the interactions of active substances with receptors. Thi...

In the present work the semi-empirical effective crystal field (ECF) method previously designed for electronic structure calculations of transition metal complexes and utilizing non-Hartree-Fock trial wave function and parameterized for complexes of doubly charged Cr2+, V2+, Mn2+, Fe2+, Co2+, and Ni2+ cations is extended to complexes of triply char...

The effective crystal field method, which allows crystal field parameters to be estimated semiempirically, can be reformulated for calculating angular overlap model parameters solely from the geometry of transition metal complexes with the use of the initial effective crystal field model parameters. The suggested procedure fairly well reproduces th...

A new approach to calculating potential energy surfaces (PEP) of various spin states of transition-metal complexes is suggested. The approach is based on description of the electronic structure of a complex within the method of effective crystalline field (ECF) in which the wave function is written as an anti-symmetrized product of the wave functio...

A series of the d6 iron(II) complexes with bulky organic ligands (like [Fe(bipy)2(NCS)2]) can exist in two spin forms: in the low-spin (S = 0) form at low temperature and in the high-spin (S = 2) form at high temperature. In the crystal phase, the transition between these two forms may be either smooth or abrupt. Recently, the abrupt spin transitio...