No abstract

Aim. Search for new inhibitors of the mitotic apparatus of mycobacterium and a number of enzymatic targets. Methods. 3D models of key targets reconstruction and geometry optimization and analysis of biologically active conformations of inhibitors were performed according to a previously developed technique. Results. A revision of mycobacterial inhibitors, which exhibit antimicrobial action against representatives of the genus Mycobacterium, was carried out, which made it possible to create an appropriate reference library of compounds. The complete spatial structure of a number of the main targets of targeted therapy for tuberculosis was reconstructed and verified, and the features of their interaction with selective inhibitors were established. Chemogenomic profiling was performed, which made it possible to draw conclusions regarding the uniqueness of the studied sites and the potential toxicity of compounds related to these sites for humans. Conclusions. A well-developed search algorithm for known inhibitors of proteins with M. tuberculosis allows further study of the features of their interaction with the corresponding homologues of M. bovis and the development of new, more selective compounds using molecular dynamics and docking methods. Keywords: tuberculosis, in silico, anti-tuberculosis drugs.

Plant systems have been considered valuable models for addressing fundamental questions of microtubule (MT) organization due to their considerable practical utility. Protein acetylation is a very common protein modification, and therate of acetylation can be modulated in cells in different biological states, and these changes can be detected at a molecular level. Here, we focused on K40, K112, and K394 residues as putative acetylation sites, which were shown to exist in both plants and mammals. Such residual effect of acetylation causes critical but unclear effect on MT stability. In turn, it was shown that acetylation indirectly affects the probability of interaction with different MAPs (Microtubule‐associated proteins). In a multiscale study using an all‐atom force field to reproduce several lattice‐forming elements found on the surface the microtubule, we assembled a fragment of a plant microtubule composed of nine tubulins and used it as a model object along with the existing human complex. Triplets of tubulins assembled in a lattice cell were then simulated for both human and plant protein complexes, using a coarse‐grained force field. We then analyzed the trajectories and identified some critical deformations of the MAP interaction surface. The initial coordinates were used to investigate the structural scenario in which autophagy‐related protein 8 (ATG8) was able to interact with the MT fragment.