Molecular Modeling

Sometimes, obtaining a crystal structure that would answer an important question may be elusive. In the absence of a crystal structure, molecular modeling can provide helpful clues regarding the structure-function properties of a particular protein molecule.

Docking is a method which predicts the preferred orientation of one molecule to a second when bound to each other to form a stable complex. The goal of protein–ligand docking is to predict the position and orientation of a ligand (a small molecule) when it is bound to a protein receptor or enzyme.

Virtual screening is the name given to the process of docking three-dimensional models of drug-like compounds into three dimensional models of potential drug receptors, usually proteins. Such computational methods are far faster, and cheaper, than physically testing tens of thousands of potential drugs in chemical or cell-based assays, which has been a standard in the pharmaceutical industry for generations. The ligands to be docked may have a number of rotatable bonds, generating a huge number of potential conformations to be examined; energetic calculations are used to rank protein-ligand interactions. Today all large pharmaceutical houses use virtual screening operations to facilitate their drug discovery programs.

Homology modeling refers to constructing an atomic-resolution model of the “target” protein from its amino acid sequence and an experimental three-dimensional structure of a related homologous protein (the “template”). Homology modeling relies on the identification of one or more known protein structures likely to resemble the structure of the query sequence, and on the production of an alignment that maps residues in the query sequence to residues in the template sequence.

Contact Art Monzingo for more information on molecular modeling services.

Description of Molecular Modeling Services

  • Ligand Docking – Preparation of a three-dimensional model of a ligand bound to the active site of a protein molecule using computational methods.
  • Virtual Screening – Docking of a library of three-dimensional models of drug-like compounds into a three-dimensional model of a potential drug receptor (usually a protein), using computational methods. Protein-ligand interactions are ranked using energetic calculations.
  • Homology Modeling – Preparation of a protein molecule based on the known structure of a homologous protein molecule using computational methods.