About
Sri Lanka is a tropical country in South Asia that consists of a variety of endemic plants. The flora of Sri Lanka comprises about 4143 flowering plants of which about 1025 (24.7%) species are endemic to the island.
Plants have played an important role in the development of medicines for curing many diseases throughout centuries. From recent studies, a large number of chemical compounds from endemic plants of Sri Lanka have been identified and structure elucidations were completed by studying the bark, timber, fruits or flowers of those plants. From the research publications of the above studies, about 200 chemical structures have been compiled for the first time in Sri Lanka. However there was no systematic study of characterizing these chemical compounds to be investigated as drug leads for known illnesses.To the best of our knowledge there is not an information system available for structure and activity properties of chemical compounds isolated from endemic and native plants of Sri Lanka. This is the first attempt to create a comprehensive information system for dissemination of structural and chemical parameters of chemical compounds identified from endemic and native plants of Sri Lanka.
In this project, the structural properties of these compounds were computationally calculated ,collected them and used in QSAR analysis. A computational approach was used to develop Molecular mechanics force field parameters for each of these molecules.Molecular mechanics force field is the essential ingredient for molecular simulation work. There are several force fields such as KBFF,CHAMM, AMBER, GROMOS that can be used for molecular modeling/simulation studies Force field of a molecule is an analytical functional form for the energy of that molecule.
The total energy of a molecular system can be given as;
Etotal = Ebond stretching + Ebending + Etortion + Edispersion + Eelectrostatics
Force field parameters means the values for equilibrium bond lengths, bond angles, dihedral angles, corresponding force constants, partial charges and van der Waals parameters .Equilibrium bond lengths, bond angles and dihedral angles along with corresponding force constants and partial charges were obtained from electronic structure calculations performed on each molecule.The GROMOS53a6 force field was used for atoms of the molecules in this project.
Computer Aided Drug Designing (CADD) represents more recent applications of computers as tools in the new drug discovery process. It must be emphasized that computers cannot be substituted for the whole drug discovery process. However, at the initial stage of randomly picking drug like molecules and conducting experiments in the lab to find their bio-activity is very expensive and time consuming. This step can be replaced by CADD. Major steps of CADD are detection of the molecular base of the disease, finding the drug lead, molecular docking, refinement of the drug lead. In a traditional way, large number of possible drug candidates would be tested in laboratory level utilizing huge amount of chemicals and large number of man hours.Due to the Developed molecular mechanics force fields for the identified molecules in the information system will benefit in wide area of research activities as the accurate force field parameters are the essential information for molecular dynamics simulation studies of such molecular systems.
Further as a benchmark study, this database will be searched computationally, to find suitable molecules that can be used as drug leads for metal ion induced illnesses such as Alzheimer’s disease.
Softwares,operating systems and online sources used in this project : Gromacs,Gaussian 09,Prodrg online server,Chemicalize online server,Rasmol,Chimera and Linux operating system.
The University of Colombo has developed this site as a PhD research project.(Research grant: AP/3/2/2014/RG/01)
