gototopgototop

Main Menu

Name:
Dr. Ashish
Expertise:
Use structure-based knowledge to design bonsai proteins of bio-medical relevance.

Contact Address:

Principal Investigator: Ashish, Ph.D.
Scientist E-1
Protein Science and Engineering Division
Institute of Microbial Technology
Sector 39-A, Chandigarh – 160036, INDIA
Phone: 0172-2636680 Ext. 3284
Fax: 0172-2690632
Email: ashgang@imtech.res.in

Write-up of research and development interests/focus, past and present goals:

Research Interests


We are trying to understand structure-function relationship of proteins using biophysical methods mainly NMR, dynamic and electrophoretic light scattering (DLS and ELS), small angle x-ray/neutron scattering (SAXS/SANS). Significant use of molecular modeling methods are also employed to gain visual insight into flexible yet functionally important regions in proteins. Our long-term goal is to employ the solution conformational properties of proteins and their complexes to design minimal versions retaining some function of the native protein.


Topics of Interest and group members

 

  • Designing molecules which will block HIV-1 mediated shape changes in the CD4 receptor: Our hypothesis is that HIV-1 entry will be derailed if the gp120 induced dramatic shape change across the CD4 receptor can be blocked. (Ashish, Juncadella, I.J., Garg, R., Boone, C.D., Anguita, J., Krueger, J.K. J Biol. Chem. 2008 283, 2781).  Using the crystal structure of the CD4 receptor, we are doing virtual screening of molecules which will dock near the flexible portion of the CD4 receptor. The high scoring molecules will be tested experimentally for their binding efficacy and specificity.
    Funding: CSIR India from 2009-2012.
    Communications
    : 1. Rathore, Y.S., Solanki, A.K., Pandey, K., Singh, S., Ashish* “Shall we target our own CD4 to block HIV-1 entry? A molecular modeling based proposition”. Under review.
  • Screening peptidic molecules which will shut-down specific pro-inflammatory pathways: Earlier, we showed the importance of the DD loops in TLR2/1 signaling (Gautam, J.K., Ashish, Comeau, L.D., Krueger, J.K., Smith, M.F. Jr. J. Biol. Chem.2006 281, 30132-42). We are now working on a hypothesis that peptides competing with the binding surfaces of DD loops offer
    a more specific way to terminate downstream signaling events.
  • Comparing solution structures of neutralizing vs. non-neutralizing antibodies: While studying solution structure of HIV-1 neutralizing antibody, IgG1 b12, we realized that the asymmetric disposition of its Fab arms relative to Fc is intrinsic to the molecule and independent of molecular packing effects.
    Communication
    : 1. Ashish*, Solanki, A.K., Boone, C.D., Krueger, J.K. “Asymmetric conformation of neutralizing antibody IgG1 b12 is retained in solution and promotes 1:1 binding with HIV-1 gp120”. Under review.
  • Shape changes which precede aggregation of GLOBULAR and GAUSSIAN-CHAIN like soluble proteins: Literature suggests that the initial association of soluble proteins capable of aggregating does not involve a detectable change in their secondary structural content. Employing theoretical and experimental methods, we will test our hypothesis that re-distribution in electrostatic surface potential precedes initial aggregation events.
  • Optimizing delivery of bio-active mini-proteins and peptides: The hurdle associated with the use of several bio-active peptides and mini-proteins is their short-life spans before reaching their site of action. Our research goals are: 1) We are interested in modifying peptides with known medical properties by introducing non-coding residues and chemical moieties to stabilize their bio-active conformation. 2) Encapsulating these native peptides and their analogs into bio-degradable nanoparticles for slow release.

Selected list of Publications and Patents:


  • Rathore, Y. S., Solanki, A. K., Dhoke, R. R. & Ashish (2011) 
    SAXS data analysis and modeling of tetravalent neutralizing antibody CD4-IgG2 -/+ HIV-1 gp120 revealed that first two gp120 bind to the same Fab arm, Biochem Biophys Res Commun. 415, 680-5.

  • Helmstadter, M., Luthy, K., Godel, M., Simons, M., Ashish, Nihalani, D., Rensing, S. A., Fischbach, K. F. & Huber, T. B. (2012) 
    Functional Study of Mammalian Neph Proteins in Drosophila melanogaster, Plos One. 7, e40300.

  • Mallik, L., Arif, E., Sharma, P., Rathore, Y. S., Wong, H. N., Holzman, L. B., Ashish & Nihalani, D. (2012) 
    Solution structure analysis of cytoplasmic domain of podocyte protein Neph1 using small/wide angle x-ray scattering (SWAXS), J Biol Chem. 287, 9441-53.

  • Peddada, N., Sagar, A., Ashish & Garg, R. (2012) 
    Plasma gelsolin: a general prognostic marker of health, Medical hypotheses. 78, 203-10.

  • Rathore, Y. S., Rehan, M., Pandey, K., Sahni, G. & Ashish (2012) 
    First structural model of full-length human tissue-plasminogen activator: a SAXS data-based modeling study, The journal of physical chemistry B. 116, 496-502.

  • Sharma, N., Pinnaka, A. K., Raje, M., Ashish., Bhattacharyya, M. S. & Roy Choudhury, A. (2012) 
    Exploitation of marine bacteria for production of gold nanoparticles, Microbial cell factories. 11, 86.

  • Singh, P. K., Chittpurna, Ashish, Sharma, V., Patil, P. B. & Korpole, S. (2012) 
    Identification, Purification and Characterization of Laterosporulin, a Novel Bacteriocin Produced by Brevibacillus sp. Strain GI-9, Plos One. 7, e31498.

  • Singh, S., Ashish & Dikshit, K. L. (2012) 
    Pro42 and Val45 of staphylokinase modulate intermolecular interactions of His43-Tyr44 pair and specificity of staphylokinase-plasmin activator complex, Febs Lett. 586, 653-8.

  • Ashish, Solanki AK, Boone CD, Krueger JK.
    Global structure of HIV-1 neutralizing antibody IgG1 b12 is asymmetric. Biochem Biophys Res Commun. 2010 Jan 1;391(1):947-51. Epub 2009 Dec 5. PubMed PMID: 19995532.

  • Dongre M, Singh NS, Dureja C, Peddada N, Solanki AK, Ashish, Raychaudhuri S.
    Evidence on How a Conserved Glycine in the Hinge Region of HapR Regulates Its DNA Binding Ability: LESSONS FROM A NATURAL VARIANT. J Biol Chem. 2011 Apr 29;286(17):15043-9. Epub 2011 Mar 7. PubMed PMID: 21383015; PubMed Central PMCID: PMC3083188.

  • Dahiya M, Singh S, Rajamohan G, Sethi D, Ashish, Dikshit KL.
    Intermolecular interactions in staphylokinase-plasmin(ogen) bimolecular complex: Function of His43 and Tyr44. FEBS Lett. 2011 Apr 16. [Epub ahead of print] PubMed PMID: 21510941.

  • Garg R, Peddada N, Sagar A, Nihalani D, Ashish.
    Visual insight into how low pH alone can induce actin severing ability in gelsolin under calcium free conditions. J Biol Chem. 2011 Jun 10;286(23):20387-97. Epub 2011 Apr 15. PMID:21498516[PubMed - in process]

Present group members:

  • Nagesh Peddada
  • Leena Mallik
  • Pankaj Sharma
  • Amin Sagar
  • Reema Dhoke

  • Ashish K. Solanki
  • Yogendra S. Rathore
  • Kalpana Pandey
  • Shikha Singh
  • Samir K. Nath
This site is best viewed in Mozilla Firefox, Internet Explorer 8 and above at screen resolution of 1024 x 768 and above.