Tensor Train Global Optimization: Application to Docking in the Configuration Space with a Large Number of Dimensions

Сулимов, А. В.; Zheltkov, Dmitry A.; Oferkin, I. V.; Kutov, Danil; Каткова, Екатерина В.; Тыртышников, Е. Е.; Сулимов, В. Б.

doi:10.1007/978-3-319-71255-0_12

Cited by 9 publications

(16 citation statements)

References 25 publications

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“…The present study demonstrates that the answer is positive: yes, it is possible to perform successfully such docking employing the novel tensor train global optimization algorithm [11]. In this study we describe the main features of this novel algorithm, the respective program SOL-P for docking flexible ligands into target proteins with moveable atoms [43] and the results of validation of the ligand positioning accuracy for a test set of 30 protein-ligand complexes [11]. However, the protein-ligand binding energy calculation is out of the scope of this work.…”

Section: Introductionmentioning

confidence: 87%

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

Сулимов

Zheltkov

Oferkin³

et al. 2017

Computational and Structural Biotechnology Journal

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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. The grid of precalculated energy potentials of probe ligand atoms in the field of the target protein atoms is not used. The energy of the protein-ligand complex for any given configuration is computed directly with the MMFF94 force field without any fitting parameters. The conformation space of the system coordinates is formed by translations and rotations of the ligand as a whole, by the ligand torsions and also by Cartesian coordinates of the selected target protein atoms. Mobility of protein and ligand atoms is taken into account in the docking process simultaneously and equally. The algorithm is realized in the novel parallel docking SOL-P program and results of its performance for a set of 30 protein-ligand complexes are presented. Dependence of the docking positioning accuracy is investigated as a function of parameters of the docking algorithm and the number of protein moveable atoms. It is shown that mobility of the protein atoms improves docking positioning accuracy. The SOL-P program is able to perform docking of a flexible ligand into the active site of the target protein with several dozens of protein moveable atoms: the native crystallized ligand pose is correctly found as the global energy minimum in the search space with 157 dimensions using 4700 CPU ∗ h at the Lomonosov supercomputer.

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Section: Introductionmentioning

confidence: 87%

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

Сулимов

Zheltkov

Oferkin³

et al. 2017

Computational and Structural Biotechnology Journal

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“…It turned out that FLM could be used for the comparison of different force fields in the docking procedure and for the investigations of effectiveness of different docking algorithms. Special energy minima indexes have been introduced which are convenient for the description of the low energy minima spectrum of protein-ligand complexes [48,60,61,[92][93][94]. In particular, the index of the minimum Near Native (INN) is useful for the indication of the docking accuracy.…”

Section: Flmmentioning

confidence: 99%

Supercomputer Docking

2019

JSFI

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This review is based on the peer-reviewed research literature including the author's own publications devoted to supercomputer docking. The general view on docking and its role at the initial stage of the rational drug design is presented. Molecules of medicine compounds selectively bind to the active site of a protein, which is responsible for the disease progression, and stop it. Docking programs perform positioning of molecules (ligands) in the active site of the protein and estimate the protein-ligand binding energy. The larger this energy is, the less concentration of the respective compound should be used to observe the desired effect. Several classical docking programs are described in short. Examples of the adaptation of existing docking programs to supercomputing and using them for virtual screening of millions of ligands are presented. Two novel generalized docking programs specially designed for multi-core docking of a single ligand on a supercomputer are described shortly. These programs find a sufficiently wide spectrum of low energy minima of a protein-ligand complex in the frame of a given force field. The quasi-docking procedure using the generalized docking program is described. Quasi-docking allows to perform docking with quantum-chemical semiempirical methods. Finally a summary is made based on the materials presented.

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“…В связи с попытками разобраться в причинах, ограничивающих точность докинга [5], недавно были разработаны несколько суперкомпьютерных параллельных (многопроцессорных) программ докинга -FLM [48][49][50], SOL-T [51] и SOL-P [52,53], в которых не используется сетка заранее рассчитанных потенциалов взаимодействия атомов лиганда с белком, и при выполнении докинга, то есть в процессе глобальной оптимизации, энергия комплекса «белок-лиганд» для любой его конфигурации вычисляется без всяких упрощений и ограничений -прямо в рамках заданного силового поля. Эти программы названы программами прямого (или бессеточного) обобщенного докинга, причем слово «обобщенный» отражает тот факт, что цель выполнения этих программ -не просто нахождение глобального минимума энергии, как это делает большинство описанных выше программ докинга, а нахождение всего спектра низкоэнергетических минимумов комплекса «белок-лиганд», включая, конечно, и глобальный минимум.…”

Section: докинг и другие методы компьютерного моделирования лекарствеunclassified

“…Эти программы названы программами прямого (или бессеточного) обобщенного докинга, причем слово «обобщенный» отражает тот факт, что цель выполнения этих программ -не просто нахождение глобального минимума энергии, как это делает большинство описанных выше программ докинга, а нахождение всего спектра низкоэнергетических минимумов комплекса «белок-лиганд», включая, конечно, и глобальный минимум. Программы FLM [48][49][50], SOL-T [51] и SOL-P [52,53] требуют уже сравнительно больших вычислительных ресурсов (сотен вычислительных ядер), существенно превосходящих вычислительные ресурсы, необходимые для обычных или классических программ докинга типа AutoDock, ICM, SOL и др. Программы FLM и SOL-T осуществляют докинг гибкого лиганда в жесткий белок, а программа SOL-P может проводить докинг гибкого лиганда в белок с выделенными подвижными атомами.…”

Section: докинг и другие методы компьютерного моделирования лекарствеunclassified

Modern methods for the development of new drugs that affect the hemostatic system

Сулимов

Kutov

Tashchilova

et al. 2019

Voprosy gematologii/onkologii i immunopatologii v pediatrii

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The blood coagulation system plays an important role in health and disease. It is a complex network of proteolytic reactions that is activated during injuries and controls the formation of a fibrin clot. Although new components and reactions have not been discovered for thirty years, during this time there has been a revolution in understanding of how this system works and what enzymes are the optimal targets for the therapy. At the same time, new methods of drug development, first of all, computer docking, which are ideally suited for the discovery of inhibitors of blood clotting enzymes, have appeared. In this review, an attempt has been made to correlate the lines of development of new ideas about the mechanisms of coagulation, new methods of searching for drugs and their combination, thanks to which now there are more and more potentially interesting molecules that can change the face of the anticoagulant therapy in the near future. In the review, molecular modeling methods, primarily docking, which are increasingly used at the initial stage of developing new drugs, the role of docking at the initial stage of developing new inhibitors are briefly considered and the structure of the active centers of factors Xa and XIa, which determines their interaction with inhibitors, are discussed in detail.

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Tensor Train Global Optimization: Application to Docking in the Configuration Space with a Large Number of Dimensions

Cited by 9 publications

References 25 publications

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

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

Supercomputer Docking

Modern methods for the development of new drugs that affect the hemostatic system

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