Understanding the Interactions of Ubiquitin-Specific Protease 7 with Its Substrates through Molecular Dynamics Simulations: Insights into the Role of Its C-Terminal Domains in Substrate Recognition.

Ubiquitin-specific protease 7 (USP7) is a deubiquitinase enzyme that plays a critical role in regulating various cellular processes by cleaving ubiquitin molecules from target proteins. The C-terminal loop (CTL) motif is a specific region at the C-terminal end of the USP7 enzyme. Recent experiments suggest that the CTL motif plays a role in USP7's catalytic activity by contributing to the enzyme's structural stability, substrate recognition, and catalytic efficiency.

Computational study of the binding orientation and affinity of noncovalent inhibitors of the papain-like protease (PLpro) from SARS-CoV-1 considering the protein flexibility by using molecular dynamics and cross-docking.

The papain-like protease (PLpro) from zoonotic coronaviruses (CoVs) has been identified as a target with an essential role in viral respiratory diseases caused by Severe Acute Respiratory Syndrome-associated coronaviruses (SARS-CoVs). The design of PLpro inhibitors has been proposed as an alternative to developing potential drugs against this disease. In this work, 67 naphthalene-derived compounds as noncovalent PLpro inhibitors were studied using molecular modeling methods.

Testing Affordable Strategies for the Computational Study of Reactivity in Cysteine Proteases: The Case of SARS-CoV-2 3CL Protease Inhibition.

Cysteine proteases are an important target for the development of inhibitors that could be used as drugs to regulate the activity of these kinds of enzymes involved in many diseases, including COVID-19. For this reason, it is important to have methodological tools that allow a detailed study of their activity and inhibition, combining computational efficiency and accuracy. We here explore the performance of different quantum mechanics/molecular mechanics methods to explore the inhibition reaction mechanism of the SARS-CoV-2 3CL protease with a hydroxymethyl ketone derivative.

LigRMSD: a web server for automatic structure matching and RMSD calculations among identical and similar compounds in protein-ligand docking.

Motivation: Root mean square deviation (RMSD) is one of the most useful and straightforward features for structural comparison between different conformations of the same molecule. Commonly, protein-ligand docking programs have included some utilities that allow the calculation of this value; however, they only work efficiently when exists a complete atom label equivalence between the evaluated conformations.

Results: We present LigRMSD, a free web-server for the automatic matching and RMSD calculations among identical or similar chemical compounds.

Structural Requirements of -alpha-Mercaptoacetyl Dipeptide (NAMdP) Inhibitors of Virulence Factor LasB: 3D-QSAR, Molecular Docking, and Interaction Fingerprint Studies.

The zinc metallopeptidase elastase (LasB) is a virulence factor of (), a pathogenic bacterium that can cause nosocomial infections. The present study relates the structural analysis of 118 -alpha-mercaptoacetyl dipeptides (NAMdPs) as LasB inhibitors. Field-based 3D-QSAR and molecular docking methods were employed to describe the essential interactions between NAMdPs and LasB binding sites, and the chemical features that determine their differential activities.

Docking, Interaction Fingerprint, and Three-Dimensional Quantitative Structure-Activity Relationship (3D-QSAR) of Sigma1 Receptor Ligands, Analogs of the Neuroprotective Agent RC-33.

The human Sigma1 receptor (S1R), which has been identified as a target with an important role in neuropsychological disorders, was first crystallized 3 years ago. Since S1R structure has no relation with another previous crystallized structures, the presence of the new crystal is an important hallmark for the design of agonists and antagonists against this important target. Some years ago, our group identified RC-33, a potent and selective S1R agonist, endowed with neuroprotective properties.

Insights into the Structural Requirements of 2(S)-Amino-6-Boronohexanoic Acid Derivatives as Arginase I Inhibitors: 3D-QSAR, Docking, and Interaction Fingerprint Studies.

Human arginase I (hARGI) is an important enzyme involved in the urea cycle; its overexpression has been associated to cardiovascular and cerebrovascular diseases. In the last years, several congeneric sets of hARGI inhibitors have been reported with possible beneficial roles for the cardiovascular system. At the same time, crystallographic data have been reported including hARGI⁻inhibitor complexes, which can be considered for the design of novel inhibitors.