Application Note - Cheminformatics
Computation of Ligand States in Preparation for Design Against
Amit Kulkarni, Ph.D., Accelrys Inc.
Swati Puri, Ph.D., Accelrys Inc.
Increasing volumes of chemical information present a significant data management challenge to drug discovery
research organizations. Such chemical information is typically chemically correct in the context of medicinal
chemistry, but not always enumerated or represented appropriately for the physiological conditions under which their
potential biological targets exist. Correct chemistry, bond orders, tautomeric states, and ionization states are
necessary before chemicals are registered in corporate databases or used for computational experiments, such as
docking, QSAR, or molecular dynamics simulation. The necessity of providing a correct representation arises when
the molecules are to be correlated with biological activities or responses ascribed to the chemical entities being
Accelrys’ Structure Checker helps to meet this challenge by ensuring consistency and quality of chemical data across
the organization. Structure Checker can automatically correct structures based on a set of customizable chemistry
rules. Accelrys Structure Checker 1.0 enhances the ability to understand and unify chemical information based on a
customizable set of Cheminformatics rules - created to validate and interpret the chemical structure. It can be used to
ensure that structures conform to specific quality standards.
Shown in this case study is one such application of Structure Checker to process ligands before docking experiments.
Structure-based drug design is the method used to identify and optimize pharmaceutical leads when an X-ray
crystallography, NMR structure, or homology model of a specific target protein is known. Virtual screening of
corporate libraries, external compound collections, and virtual compounds using various docking methods is routine
in the drug discovery proces