Research Summary

My research area mainly involves the use of molecular docking, molecular dynamics simulations and free energy calculations to the following research problems:

  • To understand drug-receptor interactions to either optimize the binding or in search of an appropriate binding site1-6.
  • To assist formulation scientists to select appropriate cyclodextrin carriers to enhance drug dissolution profiles7-10. In this area, our group is currently working on selecting appropriate parameters used in MM-PBSA and MM-GBSA to accurately predict drug/organic molecule’s binding affinity to cyclodextrins11.
  • To understand the effect of mutations on protein’s functions, structure and dynamics. This area also formed the main theme of my PhD thesis, wherein we developed a computational method to predict mutational hotspots in pharmaceutically important drug targets12. We also attempted to clarify the discrepancies in computational and experimental literature reports explaining the mechanism through which mutations cause therapeutical failure to the anticancer agent, crizotinib (anaplastic lymphoma kinase inhibitor) 13. In this line, we also sort to understand, using molecular dynamics, how do new generations of anaplastic lymphoma kinase inhibitors, brigatinib and entrectinib, bind to crizotinib-resistant anaplastic lymphoma kinase14. Also, in a collaborative effort, we sort to understand the structure and function of Flagellar Associated protein-174. This work encompasses computational prediction and validation of the FAP174 proteins and their variants and further experimental confirmation of the computational prediction. I was primarily responsible for all the computational work15.
  • To design and optimize peptides with enhanced antimicrobial profiles16.
  • Apart from my core area of research, I have also been involved in the team developing and validating new QSARs formalisms17, 18.
  • I have also been involved in lead optimization project in search of better anti-tubercular agents19. This work shows the computational screening of ligands in search for new and effective Antitubercular agents. In this work, my primary role was to search for molecules that have shown excellent activity against Tubercular bacilli, however, failed in the pharmacokinetic properties. BM212 was once such molecule which showed excellent biological activity along with severe toxicity issues. My role was to use the shape-based screening approach to identify scaffolds that could replace molecular groups responsible for the toxicity shown by BM212. The molecules that were identified in the computational screening were synthesized and biologically evaluated and were found to justify the computational hypothesis.
  • I have also been involved in lead optimization project in search of better anti-tubercular agents19. This work shows the computational screening of ligands in search for new and effective Antitubercular agents. In this work, my primary role was to search for molecules that have shown excellent activity against Tubercular bacilli, however, failed in the pharmacokinetic properties. BM212 was once such molecule which showed excellent biological activity along with severe toxicity issues. My role was to use the shape-based screening approach to identify scaffolds that could replace molecular groups responsible for the toxicity shown by BM212. The molecules that were identified in the computational screening were synthesized and biologically evaluated and were found to justify the computational hypothesis.

List of publications in line with the research summary:

1.         Pai, S.; Martis, E. A. F.; Joshi, S.; Munshi, R.; Juvekar, A. Plumbagin exerts antiobesity effects through inhibition of pancreatic lipase and adipocyte differentiation. Phytotherapy Research 2018, 32, 1631–1635.

2.         Chintakrindi, A. S.; Martis, E. A. F.; Gohil, D. J.; Kothari, S. T.; Chowdhary, A. S.; Coutinho, E. C.; Kanyalkar, M., A. A Computational Model for Docking of Noncompetitive Neuraminidase Inhibitors and Probing their Binding Interactions with Neuraminidase of Influenza Virus H5N1. Current Computer-Aided Drug Design 2016, 12, 272 – 281.

3.         Thimmaiah, K.; Ugarkar, A. G.; Martis, E. A. F.; Shaikh, M. S.; Coutinho, E. C.; Yergeri, M. C. Drug–DNA Interaction Studies of Acridone-Based Derivatives. Nucleosides, Nucleotides and Nucleic Acids 2015, 34, 309-331.

4.         Pai, S.; Martis, E. A. F.; Munshi, R.; Gursahani, M.; Mestry, S.; Juvekar, A. Chrysin exerts potential anti-obesity effects by modulating pancreatic lipase, sucrose preference and locomotor activity in rats (Submitted) 2019.

5.         Shirole, T.; Martis, E. A. F.; Makhija, D.; Pissurlenkar, R.; Jagtap, A.; Coutinho, E. PP264—4-Methylesculetin a dual acting inhibitor of acetylcholinesterase and xanthine oxidase. Clinical Therapeutics 2013, 35, e100.

6.         Martis, E. A. F.; Chandarana, R. C.; Ambre, P. K.; Pissurlenkar, R. R. S.; Coutinho; C., E. In Discovery of novel leads as dual acting inhibitors of acetylcholinesterase using pharmacophore modeling, docking consensus and 3D-QSAR studies for Alzheimer’s disease, Journal of Biotechnology and Biomaterial (3rd World Congress on biotechnology), 2012; Omics publishers: 2012; p 307.

7.         Shaikh, J.; Pradhan, R.; Dandawate, P. R.; Subramaniam, D.; Ponnurangam, S.; Martis, E. A. F.; Ranpise, N.; Coutinho, E. C.; Khan, E.; Padhye, S. Spectral and Molecular Modeling Studies on the Influence of β-Cyclodextrin and Its Derivatives on Albendazole and Its Anti-Proliferative Activity Against Pancreatic Cancer Cells. Journal of Pharmaceutical Sciences and Pharmacology 2017, 3, 1-14.

8.         Avachat, A. M.; Kulkarni, J. A.; Avachat, C. M.; Pradhan, R.; Suryawanshi, T. S.; Khan, E. M.; Martis, E. A. F.; Coutinho, E. C.; Padhaye, S. Preferential formulation of Second generation antipsychotic Asenapine as Inclusion complex with Sulphobutylether-βCD (Captisol): In vitro and In vivo Evaluation. Current Drug Delivery 2018, 15, 520-531.

9.         Jyoti, K.; Bhatia, R. K.; Martis, E. A. F.; Coutinho, E. C.; Jain, U. K.; Chandra, R.; Madan, J. Soluble curcumin amalgamated chitosan microspheres augmented drug delivery and cytotoxicity in colon cancer cells: In vitro and in vivo study. Colloids and Surfaces B: Biointerfaces 2016, 148, 674-683.

10.       Bramhane, D. M.; Kulkarni, P. A.; Martis, E. A. F.; Pissurlenkar, R. R.; Coutinho, E. C.; Nagarsenker, M. S. Characterization of pioglitazone cyclodextrin complexes: Molecular modeling to in vivo evaluation. Journal of pharmacy & bioallied sciences 2016, 8, 161-9.

11.       Ugarkar, A. G.; Martis, E. A. F.; Coutinho, E. C. Assessing the Performance of the MM-PBSA and MM-GBSA Methods in Search of Appropriate Tunable Parameters to Accurately Predict the Binding Free Energy of Cyclodextrin-drug/small molecule complexes. (Under preparation) 2019.

12.       Martis, E. A. F.; Craig, I. R.; Gohlke, H.; Coutinho, E. C. Identifying Mutational Hotspots Using Atomic Fluctuations and Multiple Sequence Alignment (Under preparation). 2019.

13.       Martis, E. A. F.; Iyer, K. R.; Gohlke, H.; Coutinho, E. C. Can Molecular simulations address the mechanism of resistance for Crizotinib? (Under preparation) 2019.

14.       Martis, E. A. F.; Coutinho, E. C. How do brigatinib and entrectinib interact with crizotinib-resistant ALK variants? (Under preparation) 2019.

15.       Yogesha, M.; Rao, V. G.; Martis, E. A. F.; Coutinho, E. C.; Gohlke, H.; Chidangil, S.; Dongre, P. M.; D’Souza, J. S. Structural features of FAP174, a MYCBP-1 orthologue from Chlamydomonas reinhardtii, revealed by computational and experimental analyses. RSC Advances 2017, 7, 51391-51402.

16.       Waghu, F. H.; Joseph, S.; Ghawali, S.; Martis, E. A. F.; Madan, T.; Venkatesh, K. V.; Idicula-Thomas, S. Designing antibacterial peptides with enhanced killing kinetics. Frontiers in Microbiology 2018, 9, 325.

17.       Martis, E. A. F.; Chandarana, R. C.; Shaikh, M. S.; Ambre, P. K.; D’Souza, J. S.; Iyer, K. R.; Coutinho, E. C.; Nandan, S. R.; Pissurlenkar, R. R. Quantifying ligand-receptor interactions for gorge-spanning acetylcholinesterase inhibitors for the treatment of Alzheimer’s disease. Journal of Biomolecular Structure and Dynamics 2015, 33, 1107-1125.

18.       Joseph, B.; Gomatam, A.; Shaikh, M.; Khedkar, V.; Martis, E. A. F.; Coutinho, E. C. Eigen Value ANalySis (EVANS) ‒ A Tool to Address Pharmacodynamic, Pharmacokinetic and Toxicity Issues: Proof of Concept Study on Pharmacodynamic Datasets. International Journal of Quantitative Structure-Property Relationships 2019, 4, 118-136.

19.       Wavhale, R. D.; Martis, E. A. F.; Ambre, P. K.; Wan, B.; Franzblau, S. G.; Iyer, K. R.; Raikuvar, K.; Macegoniuk, K., Berlicki, Luckasz; Nandan, S. R.; Coutinho, E. C. Discovery of new leads against Mycobacterium tuberculosis using Scaffold Hopping and Shape-based Similarity. Bioorganic & Medicinal Chemistry 2017, 25, 4835-4844.

Research Skills and software expertise

Vast and in-depth experience and hands-on knowledge of:

Molecular dynamics simulations:

AMBER suite and DESMOND

Free-energy Calculations

MMGBSA and MMPBSA

Structure-based and ligand-based drug design techniques

Molecular docking- GLIDE, AUTODOCK (also it’s variant idock)
Pharmacophore Modeling- Phase, Catalyst and PharmaGist
3D-QSAR- CoMFA-CoMSIA and CoRIA

Quantum mechanical methods

ORCA and Guassian (09 and 03)

Linux system administration, Installation and maintaining High-Performance computing systems

Rocks Cluster Management and CentOS

Programming Languages

Python and BASH scripting

Experimental techniques (early career experience)

UV-vis spectroscopy, HPLC analysis and 1D and 2D-NMR techniques (COSY, NOESY and ROESY)
%d bloggers like this:
www.000webhost.com