Conservation of knotted and slipknotted topology in transmembrane transporters.

The existence of nontrivial topology is well accepted in globular proteins but not in membrane proteins. Our comprehensive topological analysis of the Protein Data Bank structures reveals 18 families of transmembrane proteins with nontrivial topology, showing that they constitute a significant number of membrane proteins. Moreover, we found that they comprise one of the largest groups of secondary active transporters.

Identification of Novel CB2 Ligands through Virtual Screening and In Vitro Evaluation.

Cannabinoid receptor type 2 (CB2) is a very promising therapeutic target for a variety of potential indications. However, despite the existence of multiple high affinity CB2 ligands, none have yet been approved as a drug. Therefore, it would be beneficial to explore new chemotypes of CB2 ligands.

Amino acid variants of SARS-CoV-2 papain-like protease have impact on drug binding.

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused both a health and economic crisis around the world. Its papain-like protease (PLpro) is one of the protein targets utilized in designing new drugs that would aid vaccines in the fight against the virus. Although there are already several potential candidates for a good inhibitor of this protein, the degree of variability of the protein itself is not taken into account.

Identification of CB1 Ligands among Drugs, Phytochemicals and Natural-Like Compounds: Virtual Screening and In Vitro Verification.

Cannabinoid receptor type 1 (CB1) is an important modulator of many key physiological functions and thus a compelling molecular target. However, safe CB1 targeting is a non-trivial task. In recent years, there has been a surge of data indicating that drugs successfully used in the clinic for years (e.

Restriction of S-adenosylmethionine conformational freedom by knotted protein binding sites.

S-adenosylmethionine (SAM) is one of the most important enzyme substrates. It is vital for the function of various proteins, including large group of methyltransferases (MTs). Intriguingly, some bacterial and eukaryotic MTs, while catalysing the same reaction, possess significantly different topologies, with the former being a knotted one.

A Guide to Targeting the Endocannabinoid System in Drug Design.

The endocannabinoid system (ECS) is one of the most crucial systems in the human organism, exhibiting multi-purpose regulatory character. It is engaged in a vast array of physiological processes, including nociception, mood regulation, cognitive functions, neurogenesis and neuroprotection, appetite, lipid metabolism, as well as cell growth and proliferation. Thus, ECS proteins, including cannabinoid receptors and their endogenous ligands' synthesizing and degrading enzymes, are promising therapeutic targets.

Fullerene Derivatives of Nucleoside HIV Reverse Transcriptase Inhibitors-In Silico Activity Prediction.

Here we present new derivatives of nucleoside reverse transcriptase inhibitors with a C fullerene. The computational chemistry methods used in this study evaluate affinity of designed compounds towards the HIV-1 reverse transcriptase (RT) binding site and select the most active ones. The best of the designed compounds have superior or similar affinity to RT active site in comparison to most active test compounds, including drugs used in anti-HIV therapy.