G. Madhavi Sastry

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Structure-based virtual screening plays an important role in drug discovery and complements other screening approaches. In general, protein crystal structures are prepared prior to docking in order to add hydrogen atoms, optimize hydrogen bonds, remove atomic clashes, and perform other operations that are not part of the x-ray crystal structure refinement(More)
Virtual screening is a widely used strategy in modern drug discovery and 2D fingerprint similarity is an important tool that has been successfully applied to retrieve active compounds from large datasets. However, it is not always straightforward to select an appropriate fingerprint method and associated settings for a given problem. Here, we applied eight(More)
Shape-based methods for aligning and scoring ligands have proven to be valuable in the field of computer-aided drug design. Here, we describe a new shape-based flexible ligand superposition and virtual screening method, Phase Shape, which is shown to rapidly produce accurate 3D ligand alignments and efficiently enrich actives in virtual screening. We(More)
This study sheds new light on the role of acidic residues present in the active site cavity of human aromatase. Eight acidic residues (E129, D222, E245, E302, D309, E379, D380 and D476) lining the cavity are identified and studied using comparative modeling, docking, molecular dynamics as well as statistical techniques. The structural environment of these(More)
A systematic virtual screening study on 11 pharmaceutically relevant targets has been conducted to investigate the interrelation between 8 two-dimensional (2D) fingerprinting methods, 13 atom-typing schemes, 13 bit scaling rules, and 12 similarity metrics using the new cheminformatics package Canvas. In total, 157 872 virtual screens were performed to(More)
Comparative protein modeling, active site analysis and binding site specificity for the homologous series of plasmepsins (PM's), present in food vacuole of Plasmodium falciparum, are carried out. Four loops (L1, L2, L3 and L4), which show maximum structural deviations irrespective of type of inhibitor, have been identified. Comparison of the crystal(More)
High-temperature requirement protease A2 (HtrA2), a multitasking serine protease that is involved in critical biological functions and pathogenicity, such as apoptosis and cancer, is a potent therapeutic target. It is established that the C-terminal post-synaptic density protein, Drosophila disc large tumor suppressor, zonula occludens-1 protein (PDZ)(More)
It is proposed that the hydronium ion, H3O+, binds to the E1 conformation of the alpha-subunit of gastric proton pump. The H3O+ binding cavities are characterized parametrically based on valence, sequence, geometry, and size considerations from comparative modeling. The cavities have scope for accommodating monovalent cations of different ionic radii. The(More)
A comprehensive database named, protein ligand interaction database (PLID), is created with 6295 ligands bound to proteins extracted from the protein data bank (PDB). This is by far the most comprehensive database of physico-chemical properties, quantum mechanical descriptors and the residues present in the active site of proteins. It is a publicly(More)
The geometrical arrangement of the aromatic rings of phenylalanine, tyrosine, tryptophan and histidine has been analyzed at a database level using the X-ray crystal structure of proteins from PDB in order to find out the aromatic-aromatic (π-π) networks in proteins and to understand how these aromatic rings are connected with each-other in a specific π-π(More)