Hierarchical analysis of the target-based scoring function modification for the example of selected class A GPCRs.

Computational methods, especially molecular docking-based calculations, have become indispensable in the modern drug discovery workflow. The constantly increasing chemical space requires fast, robust but most of all highly predictive methods to search for new bioactive agents. Thus, the scoring function (SF) is a useful and broadly applied energy-based element of docking software, allowing quick and effective evaluation of a ligand's propensity to bind to selected protein targets.

Electrostatic potential and non-covalent interactions analysis for the design of selective 5-HT ligands.

Despite the significant improvement of methodology in the field of the in silico drug discovery, the search for selective drugs is still far from trivial. This is especially relevant in the case of designing new medicaments for treatment of central nervous system disorders. In this work, we present a new approach based on the molecular docking and the following electronic properties analysis of ligands' binding poses (electrostatic potential distribution analysis and quantitative topological analysis of the electron density distribution).

The engineered β-lactoglobulin with complementarity to the chlorpromazine chiral conformers.

Chlorpromazine (CPZ) is a phenothiazine acting as dopamine antagonist. Aside from application in schizophrenia therapy, chlorpromazine is found to be a putative inhibitor of proteins involved in cancers, heritable autism disorder and prion diseases. Four new β-lactoglobulin variants with double or triple substitutions: I56F/L39A, F105L/L39A, I56F/L39A/M107F or F105L/L39A/M107F changing the shape of the binding pocket were produced and their chlorpromazine binding properties have been investigated by X-ray crystallography, circular dichroism, isothermal titration calorimetry and thermophoresis.