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Add-Ons To Molecular Modeling Methods: Improvement In Activity Prediction
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ADD-ONS TO MOLECULAR MODELING METHODS: IMPROVEMENT IN ACTIVITY PREDICTION
In book
Vol. 5. , “Admiral Print” LLC, 2024.
Konshina A., Bocharov E., Konovalova E. et al., International Journal of Molecular Sciences (Швейцария) 2024 Vol. 25 No. 21 Article 11370
Non-immunoglobulin-based scaffold proteins (SPs) represent one of the key therapeutic
target-specific and high-affinity binders in modern medicine. Among their cellular targets are signaling
receptors, in particular, receptor tyrosine kinases, whose dysfunction leads to the development
of cancer and other serious diseases. Successful applications of SPs have been reported for
HER receptor type 2 (HER2), a member of the human ...
Added: December 9, 2024
Fedulova A., Armeev G., Romanova T. et al., Wiley Interdisciplinary Reviews: Computational Molecular Science 2024 Vol. 14 No. 4 Article e1728
Understanding the function of eukaryotic genomes, including the human genome, is undoubtedly one of the major scientific challenges of the 21st century. The cornerstone of eukaryotic genome organization is nucleosomes—elementary building blocks of chromatin about 10 nm in size that wrap DNA around an octamer of histone proteins. Nucleosomes are integral players in all genomic processes, ...
Added: August 29, 2024
I. V. Svitanko, Pivina T. S., Russian Chemical Bulletin 2024 Vol. 73 No. 5 P. 1093–1108
The review gives a retrospective of methods for molecular modeling of the structures, mechanisms of chemical reactions, and properties of organic compounds. The development and advancement of the ideology of preliminary modeling of the structures and formation mechanisms of reaction products in the planning of any synthesis is a relevant task in this fi eld of science. Some ...
Added: June 21, 2024
Krasavin M., Peshkov A., Lukin A. et al., International Journal of Molecular Sciences 2022 Vol. 23 No. 19 Article 11579
Starting from a screening hit, a set of analogs was synthesized based on a 4-(2-aminoethyl)piperidine core not associated previously with trace amine-associated receptor 1 (TAAR1) modulation in the literature. Several structure–activity relationship generalizations have been drawn from the observed data, some of which were corroborated by molecular modeling against the crystal structure of TAAR1. The ...
Added: February 8, 2024
Yarovaya O., Filimonov A., Baev D. et al., Viruses 2024 Vol. 16 No. 2 Article 215
Although the COVID-19 pandemic caused by SARS-CoV-2 viruses is officially over, the search for new effective agents with activity against a wide range of coronaviruses is still an important task for medical chemists and virologists. We synthesized a series of thiazolo-thiophenes based on (+)- and (−)-usnic acid and studied their ability to inhibit the main ...
Added: January 31, 2024
Rusina P., Gandalipov E., Abdyusheva Y. et al., Cancers 2023 Vol. 15 No. 15 Article 3766
General toxicity for the organism is a major drawback of anticancer drugs. Development of new generation chemotherapeutics requires the knowledge about macromolecules critical for tumor cell viability. Among these species (called therapeutic targets), the protein kinases are the established enzymes. However, the parts of protein kinases that are supposed to be targeted by drugs can ...
Added: November 1, 2023
Nikita A. Kosarim, Armeev G., Alexey K. Shaytan et al., Supercomputing Frontiers and Innovations 2022 Vol. 9 No. 2 P. 56–67
The nucleosome is the basic unit of eukaryotic DNA compaction. It consists of about 147 base pairs wrapped around an octamer of histone proteins. Nucleosomal dynamics provides the availability of packaged DNA for various factors that carry out the vital processes associated with chromatin. It is not completely known how the structure and dynamics of ...
Added: September 4, 2023
van Tilborg D., Grisoni F., Journal of Chemical Information and Modeling 2022 Vol. 62 No. 23 P. 5938–5951
Machine learning has become a crucial tool in drug discovery and chemistry at large, e.g., to predict molecular properties, such as bioactivity, with high accuracy. However, activity cliffs─pairs of molecules that are highly similar in their structure but exhibit large differences in potency─have received limited attention for their effect on model performance. Not only are these ...
Added: December 22, 2022
Medvedev M., Stroganov O., Dmitrienko A. et al., Mendeleev Communications 2022 Vol. 32 No. 6 P. 735–738
Here we propose an over-the-hood docking method that compensates for systematic errors in the docking force fields. This method explicitly estimates the interaction energy of the ligand with the protein surface and uses it as a baseline to estimate the actual binding energy in the active site. It improves the accuracy of virtual screening in the LeadFinder package by up ...
Added: October 25, 2022
Nikitiuk B., D. I. Salikova, N. D. Kondratyuk et al., Journal of Molecular Liquids 2022 Vol. 368 Article 120714
The scaling between the excess entropy and transport coefficients of liquids is an interesting property found by Rosenfeld in atomistic simulations. Later, Dzugutov proposed to estimate the excess entropy on the basis of the pair entropy. That approach has been shown to work well for atomic liquids and rigid molecules, but there is a problem ...
Added: August 9, 2022
Tararushkin E., Pisarev V., Kalinichev A. G., Cement and Concrete Research 2022 Vol. 156 Article 106759
Ettringite, (Ca6[Al(OH)6]2[SO4]3·nH2O, n = 24–27), is one of the common phases of cement and plays an important role in cement chemistry as the primary cause of sulphate corrosion in Portland cement. Molecular dynamic computer simulations have already been applied earlier to model the crystal structure of ettringite and its interfaces with aqueous salt solutions. A recently developed version of the widely ...
Added: March 28, 2022
Bocharov E. V., Gremer L., Urban A. S. et al., Journal of Medicinal Chemistry 2021 Vol. 64 No. 22 P. 16464–16479
Alzheimer’s disease (AD) is a severe neurodegenerative pathology with
no effective treatment known. Toxic amyloid-β peptide (Aβ) oligomers play a crucial
role in AD pathogenesis. All-D-Enantiomeric peptide D3 and its derivatives were
developed to disassemble and destroy cytotoxic Aβ aggregates. One of the D3-like
compounds is approaching phase II clinical trials; however, high-resolution details of its
disease-preventing or pharmacological actions ...
Added: February 1, 2022
Stroylov Viktor S., Svitanko I., Maksimenko A. et al., Bioorganic and Medicinal Chemistry Letters 2020 Vol. 30 Article 127608
The ability of monomethoxy-substituted o-diphenylisoxazoles 2a-d to interact with the colchicine site of tubulin was predicted using computational modeling, docking studies, and calculation of binding affinity. The respective molecules were synthesized in high yields by three steps reaction using easily available benzaldehydes, acetophenones, and arylnitromethanes as starting material. The calculated antitubulin effect was confirmed in vivo in a sea urchin ...
Added: December 24, 2021
Shcherbinina S., Toukach Ph., International Journal of Molecular Sciences 2020 Vol. 21 No. 20 Article 7702
Analysis and systematization of accumulated data on carbohydrate structural diversity is a subject of great interest for structural glycobiology. Despite being a challenging task, development of computational methods for efficient treatment and management of spatial (3D) structural features of carbohydrates breaks new ground in modern glycoscience. This review is dedicated to approaches of chemo- and ...
Added: October 14, 2021
Titov I., Stroylov V., Rusina P. V. et al., Russian Chemical Reviews 2021 Vol. 90 No. 7 P. 831–867
The review aims to present a classification and applicability analysis of methods for preliminary molecular modelling for targeted organic, catalytic and biocatalytic synthesis. The following three main approaches are considered as a primary classification of the methods: modelling of the target – ligand coordination without structural information on both the target and the resulting complex; ...
Added: September 25, 2021
Armeev G., Kniazeva A., Komarova G. et al., Nature Communications 2021 Vol. 12 Article 2387
Nucleosomes are elementary building blocks of chromatin in eukaryotes. They tightly wrap ∼147 DNA base pairs around an octamer of histone proteins. How nucleosome structural dynamics affect genome functioning is not completely clear. Here we report all-atom molecular dynamics simulations of nucleosome core particles at a timescale of 15 micro- seconds. At this timescale, functional modes ...
Added: September 14, 2021
Omelchuk O., Malyshev V., Medvedev M. et al., Journal of Organic Chemistry 2021 Vol. 86 No. 12 P. 7975–7986
Oligomycin A is a potent antibiotic and antitumor agent. However, its applications are restricted by its high toxicity and low bioavailability. In this study, we obtained Oligomycin A Diels− Alder adducts with benzoquinone and N-benzylmaleimide and determined their absolute configurations by combining 1H and ROESY NMR data with molecular mechanics conformational analysis and quantum chemical ...
Added: September 6, 2021
Svitanko I., Novikov F. N., Rusina P. V. et al., Mendeleev Communications 2020 Vol. 30 No. 4 P. 430–432
Although CDK7 inhibitors are considered to be potential anticancer drugs, all inhibitors developed so far have significant disadvantages preventing their further use. We have developed a new CDK7 inhibitor scaffold lacking hepatotoxicity using molecular dynamics (MD) and free energy perturbation (FEP/MD) methods, and were able to double its binding affinity after additional research. The combination ...
Added: September 6, 2020
Svitanko Igor, Stroylov V., Mendeleev Communications 2020 Vol. 30 No. 4 P. 419–420
Identification of disulfiram and neratinib as putative covalent inhibitors of SARS-CoV-2 virus main protease Mpro by a combination of 'on-top docking' procedure, expert evaluation of potential hits and molecular dynamics is reported herein. This finding shows the importance of further development of virtual screening add-ons. ...
Added: August 31, 2020