Molecular Docking of Selective Dopamine D1A Receptor Agonists: Achieving Binding Energies Exceeding –11 kcal/mol
https://zenodo.org/records/18848530
Dopamine receptor D1A agonist –11.1 kcal/mol is a flagship for docking selective and high-affinity scaffolds. The structure features an enlarged aromatic core, a compressed pro-ethylamine group in the form of imidazoline, and a cyclopentane complementary imidazole scaffold. This structure, with its special radical configuration, allows for stacking in the aromatic ring of dopamine, positioning the amino group opposite D-103, enabling fork-like docking of hydrogen and lipophilic bonds. Also, in the aromatic ring, bonds are formed with hydroxyls, ketones, or aldehydes, with syrins responsible for binding the phenolic hydroxyls of dopamine or their lipophilic adjacent amino acid residues in the presence of lipophilic radicals(figure1).
Dopamine receptor D1A agonist –11.1 kcal/mol shows a decrease in affinity on the type 2 receptor to 9.1 kcal/mol, the structure is located in the receptor with its back side up and is in a state close to false triggering(figure2). Thus, high selectivity, as well as high affinity of the structure, are a consequence of more complete agonistic filling of the receptor pocket.
Unlike the asymmetrical imidazoline core, one of the additional cores is completely symmetrical and also represents a highly available diimidazole. The symmetry of this structure, with an affinity of -10 kcal/mol (figure3), reduced selectivity at an affinity of -8.1 kcal/mol for the D2 receptor, since the amino groups of the imidazoles also formed an agonist fork(D114), and selectivity in this case is due solely to a decrease in agonism(figure4).
Dozens of structures (in the supplementary materials) systematically confirm high affinity and agonistic binding.
Molecular Docking of Selective Dopamine D1A Receptor Agonists: Achieving Binding Energies Exceeding –11 kcal/mol
https://zenodo.org/records/18848530
Dopamine receptor D1A agonist –11.1 kcal/mol is a flagship for docking selective and high-affinity scaffolds. The structure features an enlarged aromatic core, a compressed pro-ethylamine group in the form of imidazoline, and a cyclopentane complementary imidazole scaffold. This structure, with its special radical configuration, allows for stacking in the aromatic ring of dopamine, positioning the amino group opposite D-103, enabling fork-like docking of hydrogen and lipophilic bonds. Also, in the aromatic ring, bonds are formed with hydroxyls, ketones, or aldehydes, with syrins responsible for binding the phenolic hydroxyls of dopamine or their lipophilic adjacent amino acid residues in the presence of lipophilic radicals(figure1).
Dopamine receptor D1A agonist –11.1 kcal/mol shows a decrease in affinity on the type 2 receptor to 9.1 kcal/mol, the structure is located in the receptor with its back side up and is in a state close to false triggering(figure2). Thus, high selectivity, as well as high affinity of the structure, are a consequence of more complete agonistic filling of the receptor pocket.
Unlike the asymmetrical imidazoline core, one of the additional cores is completely symmetrical and also represents a highly available diimidazole. The symmetry of this structure, with an affinity of -10 kcal/mol (figure3), reduced selectivity at an affinity of -8.1 kcal/mol for the D2 receptor, since the amino groups of the imidazoles also formed an agonist fork(D114), and selectivity in this case is due solely to a decrease in agonism(figure4).
Dozens of structures (in the supplementary materials) systematically confirm high affinity and agonistic binding.
This docking demonstrates a highly repeatable dopamine geometry that occupies the entire receptor. The hydrogen bonds are identical to those found in dopamine, indicating a potent agonist. An affinity of -9.4 is an order of magnitude higher than that of the most potent dopaminergic agents and promises a starting dose of micrograms. This could be the LSD or fentanyl of dopaminergic agents.
This docking demonstrates a highly repeatable dopamine geometry that occupies the entire receptor. The hydrogen bonds are identical to those found in dopamine, indicating a potent agonist. An affinity of -8.9 is an order of magnitude higher than that of the most potent dopaminergic agents and promises a starting dose of micrograms. This could be the LSD or fentanyl of dopaminergic agents.
This docking demonstrates a highly repeatable dopamine geometry that occupies the entire receptor. The hydrogen bonds are identical to those found in dopamine, indicating a potent agonist. An affinity of -8.9 is an order of magnitude higher than that of the most potent dopaminergic agents and promises a starting dose of micrograms. This could be the LSD or fentanyl of dopaminergic agents.
Molecular Docking of Cannabinoids: Achieving Binding
Energies Exceeding –15 kcal/mol for His178 and Predicted
Potency Over HU-210. Human Cannabinoid CB1 Receptor.
Yaroslav G. Zaitsev ORCID: 0000-0002-0069-2997 Date: 03.02.2026
DOI: https://doi.org/10.5281/zenodo.18444783
E-mail nabrosovnabrosov@gmail.com
Abstract
The amino acid residue His178 mediates highly effective agonism, even in cases of flexible
binding modes as observed with HU-210. Docking analysis of the test structures revealed a
distinct network of stable interactions involving His178, Met109, K376, F108, and K367.
This configuration results in multidentate coordination and bilateral stabilization within the
deep binding pocket
Не солю, если солить, скорее после готовки и осторожно с солью и специями, а вот картофель нужно подбирать, самый вкусный, самый с небольшими зернами крахмала и помоложе.
Вкус и аромат тонкий, играет, раскрывается, немного ореха и сыра, пространство-терруар, немного масленый, томлённый.
Может быть есть потенциал при использовании вкусных сортов картофеля, с хорошего терруара...
Самый диетический метод приготовления пищи, медленное томление, но в данном продукте неожиданно разрываются не постные нотки, томление на водяной бане обогащает органолептическую составляющею картофеля.
Готовлю периодически, имеет место быть, также готовлю некоторые виды рыбы, мясо нужно будет попробовать, спаржу вигна тоже попробую на томлении, интересно как раскроется вкус, а также полезно снизить нагрузку на организм.
PayPal.. nabrosovnabrosov@gmail.com
Phone 380986003302
Подробный ролик на канале, всё гораздо более интереснее и сложнее. Это анализ, но и проект реальных препаратов, наука и бизнес. Контакты есть, пишем, работаем, получаем препарат.
PayPal.. nabrosovnabrosov@gmail.com
Phone 380986003302
Запугали родителей уроды. На подоконник выложил дыни сохнуть, собирал урожай, утром вот такое, скоро пойду за кукурузой, ждите новых шортсов, тут всё стабильно.
Not a cent was thrown into this hat: PRIVATBANK, ZAITSEV YAROSLAV. IBAN: UA763052990000026208883110804.
PayPal.. nabrosovnabrosov@gmail.com
Phone 380986003302
Видимо фонд Сороса уже всех дебилов накормил и напоил, дал работу и отчитался перед демпартией, тогда я обращаюсь прямо к Дональду Трампу, нужно завести в Украину полицию, потому что её нет, есть какие-то чуваки, одни на мопедах, другие на машинах, одни малолетки, другие многолетки, их родители видимо, которые занимаются подобной деятельностью, её прикрывают, возглавляют... Собственно у них такая работа, это их труд и это результаты их труда, строителей дебилизма.
PayPal.. nabrosovnabrosov@gmail.com
Phone 380986003302
