http://dkr.cdri.res.in:8080/xmlui/handle/123456789/29 Sun, 19 Apr 2026 13:37:08 GMT 2026-04-19T13:37:08Z http://dkr.cdri.res.in:8080/xmlui/handle/123456789/1689 Virtual screening strategies: Recent advances in the identification and design of anti-cancer agents Kumar, Vikash; Krishna, Shagun; Siddiqi, M I Virtual screening (VS) is a well-established technique, which is now routinely employed in computer aided drug designing process. VS can be broadly classified into two categories, i.e., ligand-based and structure-based approach. In recent years, VS has emerged as a time saving and cost effective technique, capable of screening millions of compounds in a user friendly manner. In the area of cancer drug design, VS methods have been widely used and helped in identifying novel molecules as potential anti-cancer agents. Both ligand-based VS (LBVS) structure-based VS (SBVS) methods have been highly useful in the identification of a number of potential anti-cancer agents exhibiting activities in nanomolar range. In tune with the rapid progress in the enhancement of computational power, VS has witnessed significant change in terms of speed and hit rate and in future it is expected that VS will be a preferential alternative to high throughput screening (HTS). This review, discusses recent trends and contribution of VS in the area of anti-cancer drug discovery. Thu, 01 Jan 2015 00:00:00 GMT http://dkr.cdri.res.in:8080/xmlui/handle/123456789/1689 2015-01-01T00:00:00Z http://dkr.cdri.res.in:8080/xmlui/handle/123456789/1661 Biochemical and Biophysical Characterization of Leishmania donovani Gamma-glutamylcysteine Synthetase Agnihotri, Pragati; Singh, S P; Shakya, A K; Pratap, J V γ-glutamylcysteine synthetase (Gcs) is a vital enzyme catalyzing the first and rate limiting step in the trypanothione biosynthesis pathway, the ATP-dependent ligation of L-Glutamate and L-Cysteine to form gamma-glutamylcysteine. The Trypanothione biosynthesis pathway is unique metabolic pathway essential for trypanosomatid survival rendering Gcs as a potential drug target. Here we report the cloning, expression, purification and characterization of L. donovani Gcs. Three other constructs of Gcs (GcsN, GcsC and GcsT) were designed on the basis of S. cerevisiae and E.coli Gcs crystal structures. The study shows Gcs possesses ATPase activity even in the absence of substrates L-glutamate and L-Cysteine. Divalent ions however plays an indispensable role in LdGcs ATPase activity. Isothermal titration calorimetry and fluorescence studies illustrates that L. donovani Gcs binds substrate in order ATP >L-glutamate> L-cysteine with Glu 92 and Arg 498 involved in ATP hydrolysis and Glu 92, Glu 55 and Arg 498 involved in glutamate binding. Homology modelling and molecular dynamic simulation studies provided the structural rationale of LdGcs catalytic activity and emphasized on the possibility of involvement of three Mg2+ ions along with Glutamates 52, 55, 92, 99, Met 322, Gln 328, Tyr 397, Lys 483, Arg 494 and Arg 498 in the catalytic function of L. donovani Gcs Fri, 01 Jan 2016 00:00:00 GMT http://dkr.cdri.res.in:8080/xmlui/handle/123456789/1661 2016-01-01T00:00:00Z http://dkr.cdri.res.in:8080/xmlui/handle/123456789/1656 Design and characterization of short antimicrobial peptides using leucine zipper templates with selectivity towards microorganisms Ahmad, Aqeel; Azmi, Sarfuddin; Srivastava, Saurabh; Kumar, Amit; Tripathi, J K; Mishra, N N; Shukla, P K; Ghosh, J K Design of antimicrobial peptides with selective activity towards microorganisms is an important step towards the development of new antimicrobial agents. Leucine zipper sequence has been implicated in cytotoxic activity of naturally occurring antimicrobial peptides; moreover, this motif has been utilized for the design of novel antimicrobial peptides with modulated cytotoxicity. To understand further the impact of substitution of amino acids at ‘a’ and/or ‘d’ position of a leucine zipper sequence of an antimicrobial peptides on its antimicrobial and cytotoxic properties four short peptides (14-residue) were designed on the basis of a leucine zipper sequence without or with replacement of leucine residues in its ‘a’ and ‘d’ positions with D-leucine or alanine or proline residue. The original short leucine zipper peptide (SLZP) and its D-leucine substituted analog, DLSA showed comparable activity against the tested Gram positive and negative bacteria and the fungal strains. The alanine substituted analog (ASA) though showed appreciable activity against the tested bacteria, it showed to some extent lower activity against the tested fungi. However, the proline substituted analog (PSA) showed lower activity against the tested bacterial or fungal strains. Interestingly, DLSA, ASA and PSA showed significantly lower cytotoxicity than SLZP against both human red blood cells (hRBCs) and murine 3T3 cells. Cytotoxic and bactericidal properties of these peptides matched with peptide-induced damage/permeabilization of mammalian cells and bacteria or their mimetic lipid vesicles suggesting cell membrane could be the target of these peptides. As evidenced by Tryptophan fluorescence and acrylamide quenching studies the peptides showed similarities either in interaction or in their localization within the bacterial membrane mimetic negatively charged lipid vesicles. Only SLZP showed localization inside the mammalian membrane mimetic zwitterionic lipid vesicles. The results show significant scope for designing antimicrobial agents with selectivity towards microorganisms by substituting leucine residues at ‘a’ and/or‘d’ positions of a leucine zipper sequence of an antimicrobial peptide with different amino acids. Wed, 01 Jan 2014 00:00:00 GMT http://dkr.cdri.res.in:8080/xmlui/handle/123456789/1656 2014-01-01T00:00:00Z http://dkr.cdri.res.in:8080/xmlui/handle/123456789/1626 Oligomerization of coronin: Implication on actin filament length in Leishmania Srivastava, Rashmi; Kajuluri, L P; Pathak, Neelam; Gupta, C M; Sahasrabuddhe, A A Coronin proteins bind with actin filaments and participate in regulation of actin-dependent processes. These proteins contain a coiled-coil domain at their C-terminus, which is responsible for their dimeric or trimeric forms. However, the functional significance of these oligomeric configurations in organizing the actin cytoskeleton is obscure. Here, we report that the Leishmania coronin exists in a higher oligomeric form through its coiled-coil domain, the truncation of which ablates the ability of Leishmania coronin to assist actin-filament formation. F-actin co-sedimentation assay using purified proteins shows that the coiled-coil domain does not interact with actin-filaments and its absence does not abrogate actin-coronin interaction. Furthermore, we show that unlike other coronins, Leishmania coronin interacts with actin-filaments through its unique region. These results provide important insights into the role of coronin oligomerization in modulating actin-network. Thu, 01 Jan 2015 00:00:00 GMT http://dkr.cdri.res.in:8080/xmlui/handle/123456789/1626 2015-01-01T00:00:00Z