Molecular modeling

We apply different computational techniques based on the knowledge of the three-dimensional structure of a therapeutic target:

• Homology modeling: construction of 3D models of therapeutic targets, based on their amino acid sequence and sequences of three-dimensional structures experimentally determined from one or several related homologous proteins.
• Pharmacophore modeling: pharmacophores are defined as the set of steric and electronic features of the molecules that ensure optimal supramolecular interactions with a specific biological target, thus activating (or blocking) a biological response. In ProtoQSAR we develop pharmacophore hypotheses based on the structures of ligands and/or receptors. Subsequently, with these pharmacophores we can screen our computer databases in order to find candidates with the chemical features that best fit these hypotheses.
• Docking: computational determination of the optimal conformation and orientation of a small molecule to bind to a receptor protein and generate a stable complex in which the free energy of the complete system is minimized.
• Molecular dynamics: computational simulation of molecular interactions over short periods of time. These studies allow an approximate view of the movement of proteins and biomolecules during their interaction.
• Virtual screening: application of computational models (pharmacophoric or docking) to collections of molecular structures for the identification of those that have a greater probability of being “active”. The molecular collections may be composed of client-owned compounds, commercial libraries, or even “virtual” libraries (e.g. novel structures that have not yet been synthesized). These collections can be formed by a very variable number of structures, from a few tens to thousands or millions of them, since the rapidity of the computational analysis allow their scoring and ranking in a very short lapse of time.