SANJEEVINI (A Complete Drug Designing Software Suite)

SANJEEVINI (A Complete Drug Designing Software Suite)

    SANJEEVINI software has been developed as a computational pathway paving the way expressly towards automating lead design, making any number of known or new candidate molecules out of a small but versatile set of building blocks called templates, screening them for drug likeness, optimizing their geometry, determine partial atomic charges and assigning other force field parameters (Prof B. Jayaram & Co-workers., 2011). Docking the candidates in the active site of a given biological target , estimating the interaction/binding energy, performing molecular dynamics simulations with explicit solvent and salt on the biomolecule target, the candidate and the complex followed by a rigorous analysis of the binding free energy for further optimization.

     Recently, they have coupled Sanjeevini with AMBER and GAMESS for molecular mechanics and quantum mechanics calculations, respectively. There are total of six modules which makes Sanjeevini a complete drug design software. The source codes for all modules are written in FORTRAN, C and C++ computer languages with numerous interfacial UNIX based shell scripts which makes all the modules work like a pipeline such that output of the previous step becomes the input for the next step. The modules under Sanjeevini can also be used independent of the pathway.

The Six SANJEEVINI Modules

Module 1 : Template Library
Chemical templates are conceived as building blocks/structural frameworks for assembly and generation of new molecules

Module 2 : Molecule Generator
As a step towards de novo lead design, candidates are generated from chemical templates introduced in previous step

Module 3: Molecular Descriptors and drug like filters
A successfully lead discovery strategy must ensure bio-availaibility from the very start in generating leads while eliminating wrong candidates from considerations

Module 4: Molecular Docking
The drug activity is obtained through the molecular binding of one molecule(the ligand) to the active site of another molecular(the receptor), which in majority of cases is a protein. Computer aided methods at this stage involves- Docking and Scoring

Module 5: Energy Minimization of the Resultant Complexes
The structures of the complexes generated above are subjected to energy minimization (1000 steps of hydrogen minimization followed by 2000 steps of all atom minimization) using the SANDER module of the AMBER molecular modelling package (50).

Module 6: Binding Affinity Computations on Energy Minimized Complexes
The statistical mechanics of binding and approximations inherent in elucidating free energies from single points in configuration space are assessed.

                                       

SANJEEVINI Pathway: Active site directed lead compound molecule in silico.

       Apart from that, SANJEEVINI is also is comprehensive active site directed lead compound design software, based on the on-going research in their laboratory. The computational pathway integrates several protocols proceeding from the design of chemical templates to lead-like molecules, given the three dimensional structure of the target protein and a definition of its active site (Prof B. Jayaram & Co-workers., 2011). A conscious attempt has been made to handle the target biomolecule and the candidate drug molecules at the atomic level retaining system independence while providing access for systematic improvements at the force field level. Concerns related to geometry of the molecules, partial atomic charges, docking of candidates in the active site, flexibility and solvent effects are accounted for at the current state-of-the-art. To ensure theoretical rigor, binding free energy estimates are developed for candidate molecules with the target protein within the framework of statistical mechanics