Molecular Docking of Chiral Drug Enantiomers With Different Bioactivities.

Chirality has an important role in the drug design because enantiomers may exhibit different bioactivity when interacting with macromolecules of a living organism. In our previous work, based on the analysis of a set of 100 chiral drugs, a relationship was established between the sign of chirality of enantiomers and their bioactivity. To understand the reasons for the observed patterns of chiral specificity of drug enantiomers, the interaction of 10 enantiomeric pairs of chiral drugs with the corresponding target proteins has been considered using molecular docking and further postprocessing by quantum chemistry methods.

Design, Synthesis, and Evaluation of New Hybrid Derivatives of 5,6-Dihydro-4-pyrrolo[3,2,1-]quinolin-2(1)-one as Potential Dual Inhibitors of Blood Coagulation Factors Xa and XIa.

Cardiovascular diseases caused by blood coagulation system disorders are one of the leading causes of morbidity and mortality in the world. Research shows that blood clotting factors are involved in these thrombotic processes. Among them, factor Xa occupies a key position in the blood coagulation cascade.

Chemical Adjustment of Fibrinolysis.

Fibrinolysis is the process of the fibrin-platelet clot dissolution initiated after bleeding has been stopped. It is regulated by a cascade of proteolytic enzymes with plasmin at its core. In pathological cases, the balance of normal clot formation and dissolution is replaced by a too rapid lysis, leading to bleeding, or an insufficient one, leading to an increased thrombotic risk.

Atomistic Simulation of Physical Vapor Deposition of Optical Thin Films.

A review of the methods and results of atomistic modeling of the deposition of thin optical films and a calculation of their characteristics is presented. The simulation of various processes in a vacuum chamber, including target sputtering and the formation of film layers, is considered. Methods for calculating the structural, mechanical, optical, and electronic properties of thin optical films and film-forming materials are discussed.

New Hybrid Tetrahydropyrrolo[3,2,1-]quinolin-1-ylidene-2-thioxothiazolidin-4-ones as New Inhibitors of Factor Xa and Factor XIa: Design, Synthesis, and In Silico and Experimental Evaluation.

Despite extensive research in the field of thrombotic diseases, the prevention of blood clots remains an important area of study. Therefore, the development of new anticoagulant drugs with better therapeutic profiles and fewer side effects to combat thrombus formation is still needed. Herein, we report the synthesis and evaluation of novel pyrroloquinolinedione-based rhodanine derivatives, which were chosen from 24 developed derivatives by docking as potential molecules to inhibit the clotting factors Xa and XIa.

New Aspects of the Reaction of Thioacetamide and N-Substituted Maleimides.

N-Arylmaleimides are universal substrates for the synthesis of various heterocyclic compounds with a wide spectrum of biological activity. However, their reactions with thioacetamides have not been comprehensively studied. We studied the reactions of thioacetamide with N-arylmaleimides under various conditions.

Molecular Dynamics Simulation of Laser Induced Heating of Silicon Dioxide Thin Films.

The full-atomistic classical molecular dynamics simulation of the laser heating of silicon dioxide thin films is performed. Both dense isotropic films and porous anisotropic films are investigated. It is assumed that heating occurs due to nodal structural defects, which are currently considered one of the possible causes of laser induced damage.

Docking Paradigm in Drug Design.

Docking is in demand for the rational computer aided structure based drug design. A review of docking methods and programs is presented. Different types of docking programs are described.

Advances in Docking.

Background: Design of small molecules which are able to bind to the protein responsible for a disease is the key step of the entire process of the new medicine discovery. Atomistic computer modeling can significantly improve effectiveness of such design. The accurate calculation of the free energy of binding a small molecule (a ligand) to the target protein is the most important problem of such modeling.

New generation of docking programs: Supercomputer validation of force fields and quantum-chemical methods for docking.

Discovery of new inhibitors of the protein associated with a given disease is the initial and most important stage of the whole process of the rational development of new pharmaceutical substances. New inhibitors block the active site of the target protein and the disease is cured. Computer-aided molecular modeling can considerably increase effectiveness of new inhibitors development.

Evaluation of the novel algorithm of flexible ligand docking with moveable target-protein atoms.

We present the novel docking algorithm based on the Tensor Train decomposition and the TT-Cross global optimization. The algorithm is applied to the docking problem with flexible ligand and moveable protein atoms. The energy of the protein-ligand complex is calculated in the frame of the MMFF94 force field in vacuum.

Evaluation of Docking Target Functions by the Comprehensive Investigation of Protein-Ligand Energy Minima.

The adequate choice of the docking target function impacts the accuracy of the ligand positioning as well as the accuracy of the protein-ligand binding energy calculation. To evaluate a docking target function we compared positions of its minima with the experimentally known pose of the ligand in the protein active site. We evaluated five docking target functions based on either the MMFF94 force field or the PM7 quantum-chemical method with or without implicit solvent models: PCM, COSMO, and SGB.

Application of Molecular Modeling to Development of New Factor Xa Inhibitors.

In consequence of the key role of factor Xa in the clotting cascade and absence of its activity in the processes that do not affect coagulation, this protein is an attractive target for development of new blood coagulation inhibitors. Factor Xa is more effective and convenient target for creation of anticoagulants than thrombin, inhibition of which may cause some side effects. This study is aimed at finding new inhibitors of factor Xa by molecular computer modeling including docking SOL and postdocking optimization DISCORE programs.

Application of the docking program SOL for CSAR benchmark.

This paper is devoted to results obtained by the docking program SOL and the post-processing program DISCORE at the CSAR benchmark. SOL and DISCORE programs are described. SOL is the original docking program developed on the basis of the genetic algorithm, MMFF94 force field, rigid protein, precalculated energy grid including desolvation in the frame of simplified GB model, vdW, and electrostatic interactions and taking into account the ligand internal strain energy.

On the origin of near-IR luminescence in Bi-doped materials (II). Subvalent monocation Bi⁺ and cluster Bi₅³⁺ luminescence in AlCl₃/ZnCl₂/BiCl₃ chloride glass.

Broadband NIR photoluminescence (from 1000 to 2500 nm) was observed from partially reduced AlCl₃/ZnCl₂/BiCl₃ glass, containing subvalent bismuth species. The luminescence consists of three bands, assigned to Bi⁺ , Bi₂⁴⁺, and Bi₅³⁺ ions. The physical and optical characteristics of these centers and possible contribution to NIR luminescence from bismuth-doped oxide glasses are discussed.

New synthetic thrombin inhibitors: molecular design and experimental verification.

Background: The development of new anticoagulants is an important goal for the improvement of thromboses treatments.

Objectives: The design, synthesis and experimental testing of new safe and effective small molecule direct thrombin inhibitors for intravenous administration.

Methods: Computer-aided molecular design of new thrombin inhibitors was performed using our original docking program SOL, which is based on the genetic algorithm of global energy minimization in the framework of a Merck Molecular Force Field.

Ab initio calculation of torsion and inversion barriers of the amino group in aminopyrimidines.

Calculations of the barriers to internal rotation and inversion of the amino group in substituted pyrimidines have been performed. Torsion and inversion barriers were determined by several ab initio methods: HF, HF/MP2, MP4, CISD, QCISD, QCISD(T), CCSD, and CCSD(T). DFT method also employed.

Computation of hydration free energies of organic solutes with an implicit water model.

A new approach for computing hydration free energies DeltaG(solv) of organic solutes is formulated and parameterized. The method combines a conventional PCM (polarizable continuum model) computation for the electrostatic component DeltaG(el) of DeltaG(solv) and a specially detailed algorithm for treating the complementary nonelectrostatic contributions (DeltaG(nel)). The novel features include the following: (a) two different cavities are used for treating DeltaG(el) and DeltaG(nel).