Abstract: Isoniazid is one of the front-line drugs in the treatment of tuberculosis for many years and the mechanism of the action of the drugs still not clear. Herein we report the synthesis, QSAR model study and biological effects of ester and thioester derivatives of isonicotinic acid (INA) on different strains of Mycobacterium tuberculosis in an attempt to establish the mode of action of the active form of Isoniazid (INH). The esters of INA is expected to show antibiotic activities against strains of Mycobacterium tuberculosis upon activation by intracellular non-specific esterases, while thioesters should not show antimicrobial effects and thus served as the negative control. The results indicated that the synthesized esters did not show antimicrobial activity. Hence, the conclusion drawn is that INA is not the active form of INH. Hence more studies are necessary to search for the possible active form of isoniazid.

Abstract: We will describe the science discovered by some of the community of researchers using the SEAGrid Science gateway using computational chemistry applications. Specific science projects to be discussed include calcium carbonate and bicorbonate hydrochemistry, graphene application modeling, photonic properties of some heavy metal complexes, mechanistic studies of redox proteins and diffraction modeling of metal and metal-oxide structures and interfaces. The modeling studies involve a variety of computational techniques and coupled execution of a workflows using specific set of applications enabled in the SEAGrid Science Gateway. The integration of applications and resources that enable workflows that integrate empirical, semi-empirical ab initio and DFT and perturbative ab initio techniques through a single point of access will be presented. SEAGrid gateway hitherto used Computational Chemistry Grid middlware infrastructure and provided GridChem desktop client for users to interact with the resources and services. This deployment suffers from maintainging unsupported service architectures and system specific scripts. Going forward, the services will be outsourced to the Apache Airavata infrastructure to gain from a sustainable and more easily maintaiable set of services. As part of the new deployment we will also provide a web browser based SEAGrid Portal in addition to the SEAGrid desktop application based on the previous GridChem client. We will elaborate the services and their enhancement in this process to exemplify how the new implementation will enhance the maintainability and sustainability. We will also provide exemplar science workflows and contrast how they are supported in the new deployment relative to the previous deployment to show case the adoptability and user support for services and resources.

Abstract: Algorithms with linear-scaling (O(N)) computational complexity for Kohn-Sham density functional theory (K-S DFT) is crucial for studying molecular systems beyond thousands of atoms. A typical cross-over point of an O(N) method with an cubic-scaling method lies between 600 − 1000 atoms. Of the O(N) methods that use a polynomial-based approximation of the density matrix, the linear-scaling spectral Gauss quadrature (LSSGQ) method (Suryanarayana, JMPS, 2013) has been shown to exhibit the fastest convergence. The LSSGQ method requires a Lanczos procedure at every node in a real-space mesh, leading to a large computational pre-factor. With the goal of reducing the computational pre-factor of the LSSGQ method, and consequently its cross-over point with an O(N3) method, we propose a new interpolation scheme specific to the LSSGQ method that lift the need to perform a Lanczos procedure at every node in the real-mesh. This interpolation will be referred to as subspace interpolation. The key idea behind subspace interpolation is that there is a large overlap in the Krylov-subspaces produced by the Lanczos procedures of nodes that are close in real-space. This overlap is more pronounced in a collection of nodes where the electron density of the system is not varying much spatially. The subspace interpolation scheme takes advantage of the block-Lanczos procedure to group the Krylov-subspaces from a few representative nodes to approximate the density matrix over a larger collection of nodes; reducing the number of nodes on which the Lanczos procedure has to be performed. Subspace interpolation outperforms cubic-spline interpolation by several orders of magnitude.