Dr. Alpesh Malde

Alpeshkumar MALDE
Automated Topology Builder (ATB) and Repository for the GROMOS family of force fields
http://compbio.biosci.uq.edu.au/atb/

Orientation of L-Ser in the crystal structure 2HKZ could explain selectivity over L-Thr but could not explain enantiomeric selectivity towards D-amino acids.

Thermodynamically stable binding mode revealed by MD simulations and validated by FE calculations could explain both the selectivity as well as the mechanism of enantiomeric selectivity of family of aminoacyl-t-RNA synthetases. http://pubs.acs.org/doi/abs/10.1021/ja9002124

Research Interests

• Small molecule and biomolecular modeling: Molecular dynamics (MD) simulations, free energy (FE) and quantum mechanical (QM) calculations
  

• Force field for heteromolecular ligands and parameterization: Automated force field Topology Builder ATB and Repository
  

• Binding modes of ligands in X-ray crystal complexes
  

• Computational method development in drug design: High throughput free energy calculations
  

Projects

• SAMPL3 challenge using ATB and GROMOS/GROMACS with G53A6 Force Field
  

• VALIDATION of ATB
  

• Deriving force constants for bonded terms from a HESSIAN matrix
  

• Modeling family B G-protein Coupled Receptors (B-GPCR):ligand interactions including Gastric Inhibitory pepetide (GIP), Glucagon-like Peptide-1 (GLP-1) and Exenatide (Byetta) ] ]
  

• Binding mode of WARFARIN
  

• Single step high throughput FREE ENERGY calculations
  

• Force field for BORON and Organoboranes
  

Research Grants

“Automated Topology Builder: Force field parameterization and validation for heteromolecules“. University of Queensland Early Career Researcher (UQ-ECR), 2010, AUD 16K

“Development of methodology for high throughput free energy calculations in drug design Applications”. Australian Research Council (ARC) Discovery Project, 2009-2011, AUD 259K.

“Homology modeling of dihydroorotate dehydrogenase from Plasmodium falciparum for the purpose of designing selective inhibitors”, CSIR (Council of Scientific and Industrial Research, India), 2005-2007

Awards and Fellowships

2011
University of Queensland ResTeach Award
2010
University of Queensland Early Career Researcher (UQ-ECR) Award
2009-2011
ARC Australian Postdoctoral (ARC-APD) Fellowship
2006
IBM-Zerner Fellowship, Travel grant from CSIR, India and DST (Department of Science and Technology), India to attend Sanibel Symposium 2006 at Florida, USA
2004-2006
Senior Research Fellowship from CSIR, India
2003-2004
Project Associateship from UGC (Universities Grants Commission), India
2002-2003
Senior Research Fellowship from CSIR, India under NMITLI project on Bioinformatics
2000-2001
UGC Fellowship during M.S. (Pharm) and Gold Medal for M. S. (Pharm)
1999, 2000
Best Student Award during Third and Final year B. Pharm
1996-2000
Scholarships during all four years of B. Pharm, IPA (Indian Pharmaceutical Association) Gold Medal.

Academic

PhD (Pharmaceutical Chemistry), Bombay College of Pharmacy, University of Mumbai, India 2006
MS (Pharm) (Medicinal Chemistry) National Institute of Pharmaceutical Education and Research (NIPER), India 2001
B. Pharm. Bombay College of Pharmacy, University of Mumbai, India 2000

Positions

2009-present
ARC Australian Postdoctoral (ARC-APD) Fellow, MD group, SCMB, University of Queensland
2007-2008
Postdoctoral Research Fellow, MD Group, SCMB, University of Queensland
2003-2006
PhD Student, Bombay College of Pharmacy (University of Mumbai)
2002-2003
Senior Research Fellow, Dept of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Mohali, India
2002
Chemist, Molecular Modelling and Drug Design Lab, Dr. Reddy’s Research Foundation, Hyderabad, India
2000-2001
M.S. Student, NIPER, India

Publications

http://network.nature.com/people/U3E2C3D2E/profile

Research Articles

31. Malde AK and Mark AE. Challenges in determining the binding modes of non-standard ligands in X-ray crystal complexes. Journal of Computer-Aided Molecular Design, 2011, 25, 1-12. DOI: 10.1007/s10822-010-9397-6

30. Song B, Kibler P, Malde A, Kodukula K, Galande, A. Design of a short linear peptide that shows hydrogen bond stabilized conformation in water. Journal of the American Chemical Society, 2010, 132, 4508-4509 DOI: 10.1021/ja905341p

29. Verma J, Malde A, Khedkar S, Iyer R, Coutinho E. Local Similarity Index Analysis (LISA) – a 3D-QSAR formalism based on local molecular similarity. Journal of Chemical Information and Modelling, 2009, 49, 2695-2707. DOI: 10.1021/ci900224u

28. Malde AK and Mark AE. The Binding and Enantiomeric Selectivity of Threonyl-tRNA Synthetase. Journal of the American Chemical Society, 2009, 131, 3848-3849. DOI: 10.1021/ja9002124

27. Manvar A, Malde A, Verma J, Mishra A, Upadhyay K, Virsodia V, Acharya H, Coutinho E, Shah A. Synthesis, Anti-tubercular Activity and 3D-QSAR Study of Coumarin-4-acetic acid benzylidene hydrazides European Journal of Medicinal Chemistry, 2008, 43, 2395.

26. Verma J, Khedkar V, Khedkar SA, Malde AK, Prabhu A, Coutinho EC. “A Comprehensive Analysis of the Thermodynamic Events involved in Ligand-Receptor Binding using CoRIA and its variants”. Journal of Computer-Aided Molecular Design, 2008, 22, 91-104. DOI: 10.1007/s10822-008-9172-0

25. Khedkar SA, Malde AK, Coutinho EC. “Design of Inhibitors against MurF Enzyme of S. pneumoniae using Docking, 3D-QSAR and De Novo Design”. Journal of Chemical Information & Modeling, 2007, 47, 1839-1846.

24. Khedkar SA, Malde AK, Coutinho EC. “Inhibition of methionine-S-adenosyltransferase of M. smegmatis and M. tuberculosis: Homology Modelling, Docking and De novo Inhibitor Design”. Internet Electronic Journal of Molecular Design, 2007, 6, 151-166.

23. Khedkar SA, Malde AK, Coutinho EC. “CoMFA Study of Distamycin Analogs Binding to the Minor-groove of DNA: A Unified Model for Broad-spectrum Activity”. Journal of Molecular Modeling, 2007, 13, 1099-1108.

22. Malde AK, Khedkar SA, Coutinho EC. “The B(OH)-NH Isostere is a Surrogate for the Amide bond (CO-NH) in Peptides: An Ab Initio Study”. Journal of Chemical Theory and Computation, 2007, 3, 619-627. DOI: 10.1021/ct600256s

21. Malde AK, Srivastava SS, Coutinho EC. “Understanding Interactions of Gastric Inhibitory Peptide (GIP) with its Receptor through NMR and Molecular Modelling”. Journal of Peptide Science, 2007, 13, 287-300. DOI: 10.1002/psc.839

20. Pissurlenkar RRS, Malde AK, Khedkar SA, Coutinho EC. “Encoding Type and Position in Peptide QSAR: Application to peptides binding to Class I MHC Molecule HLA-A*0201”. QSAR and Combinatorial Science (QCS), 2007, 26, 189–203.

19. Malde AK, Khedkar SA, Coutinho EC. “Isosteres of Peptides – Boron analogs as Dipolar forms of α-amino acids: An Ab Initio Study”. Journal of Physical Organic Chemistry, 2006, 19, 1–10. DOI: 10.1002/poc.1139

18. Nayyar A, Monga V, Malde A, Coutinho E, Jain R. “Synthesis, Anti-tuberculosis Activity and 3D-QSAR Study of 4-Adamantan-1-yl group Containing 2-Substituted Quinolines”. Bioorganic & Medicinal Chemistry, 2007, 15, 626-640.

17. Malde AK, Khedkar SA, Coutinho EC. “Stationary points on the PES of N-methoxy Peptides and their Boron Isosteres: An Ab Initio Study”. Journal of Chemical Theory and Computation, 2006, 2, 1664–1674.

16. Datar PA, Khedkar SA, Malde AK and Coutinho EC. “Comparative Residue Interaction Analysis (CoRIA): A 3D-QSAR Approach to Explore the Binding Contributions of Active Site Residues with Ligands”. Journal of Computer-Aided Molecular Design, 2006, 20, 343–360. DOI: 10.1007/s10822-006-9051-5

15. Jadhav GS, Patel AR, Vavia PR, Malde AK and Coutinho EC. “Interaction of Valdecoxib with Beta Cyclodextrin: Experimental and Molecular Modeling Studies”. Journal of Inclusion Phenomenon and Macrocyclic Chemistry, 2006, 56, 261-273.

14. Nayyar A, Malde A, Coutinho E, Jain R. “Synthesis, Anti-tubercular Activity, and 3D-QSAR Study of Ring-Substituted-2/4-Quinolincarbaldehyde Derivatives”. Bioorganic & Medicinal Chemistry, 2006, 14, 7302-7310.

13. Malde AK, Khedkar SA, Coutinho EC. “The ω, φ, and ψ space of N-hydroxy-N-methylacetamide and N-acetyl-N’-hydroxy-N’-methylamide of alanine and their boron isosteres”. Journal of Chemical Theory and Computation, 2006, 2, 312-321.

12. Khedkar SA, Malde AK, Coutinho EC. “Topology of Human Methionine S-Adenosyltransferase”. Indian Journal of Chemistry A, 2006, 45A, 138-145.

11. Nayyar A, Malde A, Coutinho E, Jain R. “Three-dimensional Quantitative Structure (3D-QSAR) Activity Relationship Studies on Ring-substituted Quinoline Class of Anti-tuberculosis Agents”. Bioorganic & Medicinal Chemistry, 2006, 14, 847-856. DOI: 10.1016/j.bmc.2005.09.018

10. Khedkar SA, Malde AK, Coutinho EC. “Modeling Human Neurokinin-1 Receptor Structure using the Crystal Structure of Bovine Rhodopsin”. Internet Electronic Journal of Molecular Design, 2005, 4, 329-341.

9. Prabhu A, Malde A, Srivastava S, Coutinho E. “Solution Conformation of Substance P Antagonists – [D-Arg1, D-Trp7,9, Leu11]-SP, [D-Arg1, D-Pro2, D-Trp7,9, Leu11]-SP and [D-Pro2, D-Trp7,9]-SP by CD, NMR and MD simulations”. Peptides, 2005, 26, 875-885.

8. Khedkar SA, Malde AK, Coutinho EC. “Comparative Protein Modeling of Methionine S-Adenosyltransferase (MAT) Enzyme from M. tuberculosis: A Potential Target for Antituberculosis Drug Discovery”. Journal of Molecular Graphics and Modelling, 2005, 23(4), 355-366.

7. Malde AK, Khedkar SA, Coutinho EC, Saran A. “Geometry, Transition States and Vibrational Spectra of Boron Isostere of N-methylacetamide by ab initio calculations”. International Journal of Quantum Chemistry, 2005, 102, 734-742.

6. Bharatam PV, Iqbal P, Malde A, Tiwari R. “Electron Delocalization in Aminoguanidines”. Journal of Physical Chemistry A, 2004, 108, 10509-10517. DOI: 10.1021/jp049366e

5. Mittal S, Malde AK, Selvam C, Arun KHS, Johar PS, Jachak S, Ramarao P, Bharatam PV and Chawla HPS. “Synthesis and Evaluation of S-4-(3-thienyl)phenyl-α-methylacetic acid”. Bioorganic & Medicinal Chemistry Letters, 2004, 14 (4), 979-982.

4. Chakraborti AK, Gopalakrishnan B, Sobhia ME, Malde AK. “3D-QSAR Studies of Indole Derivatives as Phosphodiesterase IV Inhibitors”. European Journal of Medicinal Chemistry, 2003, 38 (11,12), 975-982.

3. Pal M, Madan M, Padakanti S, Pattabiraman V, Kalleda S, Vanguri A, Mullangi R, Mamidi NVS, Casturi S, Malde AK, Gopalakrishnan B and Yeleswarapu KR. “Synthesis and Cyclooxygenase-2 Inhibiting Property of 1,5-Diarylpyrazoles with Substituted Benzenesulphonamide Moiety as Pharmacophore: Preparation of Sodium Salt for Injectable Formulation”. Journal of Medicinal Chemistry, 2003, 46 (19), 3975-3984.

2. Chakraborti AK, Gopalakrishnan B, Sobhia ME, Malde AK. “Comparative Molecular Field Analysis (CoMFA) of Phthalazine Derivatives as Phosphodiesterase IV Inhibitors”. Bioorganic & Medicinal Chemistry Letters, 2003, 13 (15), 2473-2479.

1. Chakraborti AK, Gopalakrishnan B, Sobhia ME, Malde AK. “3D-QSAR Studies on Thieno[3,2-d]pyrimidines as Phosphodiesterase IV Inhibitors”. Bioorganic & Medicinal Chemistry Letters, 2003, 13 (8), 1403-1408.

Review Articles

3. Khedkar SA, Malde AK, Coutinho EC and Srivastava S. “Pharmacophore Modelling in Drug Design and Discovery: An Overview”. Medicinal Chemistry, 2007, 3, 187-197.

2. Khedkar SA, Malde AK and Coutinho EC. “In Silico screening of Ligand Databases: Methods and Applications”. Indian Journal of Pharmaceutical Sciences, 2007, 68, 689-696.

1. Malde AK and Galande A. “Combinatorial Libraries of Peptides, Peptoids and Cyclic Peptides”. Indian Drugs, 1999, 36 (10), 619-627.

Presentations

Invited talks
"Ligands in X-ray Crystal Complexes: A Drug Design Precautionary Tale". 61st Indian Pharmaceutical Congress 2009, 11-13 December 2009, Ahmedabad, India.

“Comparative Molecular Field Analysis (CoMFA): Method and Applications.” Invited talk at Workshop on Computational techniques in Drug Development at Molecular Mechanisms of Disease and Drug Action (MMDDA-2005) Conference on November 15, 2005 at Saha Institute of Nuclear Physics, Kolkata, India.

Oral Presentations
"Automated Topology Builder (ATB) and Repository for the GROMOS family of force fields". MM 2010 - Advances in Biomolecular and Materials Modelling, 28 Nov - 1 Dec 2010, Monash Institute of Pharmaceutical Sciences, Melbourne, Australia.

“Ligands in X-ray Complexes: A Drug Design Precautionary tale”. MM 2009 Molecular Modelling from Dynamical, Biomolecular and Materials Nanotechnology Perspective, 26 – 29 July 2009 at Gold Coast, Australia.

“The Omega Space of N-methylacetamide, N-hydroxy-N-methylacetamide and its Boron Isostere”. Oral presentation at National Symposium on Recent Trends in Molecular and Medical Biophysics (Indian Biophysics Society) organized by University of Pune during January 22 – 25, 2005 at Pune, India.

“Solution conformation of Gastric Inhibitory Polypeptide (GIP) (1-30 amide) by NMR and MD Simulations”. National Symposium on Advances in Magnetic Resonance and its Applications & 12th National Magnetic Resonance Society (NMRS) Meeting during October 8-11, 2005 at Gulmarg, Kashmir and RRL, Jammu, India.

Poster Presentations
“How much can we trust the binding modes of non-standard ligands in X-ray crystal complexes?”. Gordon Research Conference – Computational Chemistry 2010, Aug 29 – Sept 3 at Les Diablerets, Switzerland.

“High Throughput Free Energy Calculations: Application to Solvation Free Energy Estimation”. Poster presentation at World Association of Theoretical and Computational Chemists (WATOC) 2008, during September 14 – 19 at Sydney Convention and Exhibition Center, Australia.

“The ω, φ, and ψ Preferences of Boron Peptides”. Poster presentation at 46th Sanibel Symposium organized by the Quantum Theory Project (QTP) group of University Florida, USA during 26 February – 3 March 2006 at St. Simon’s Island, Georgia, USA.

“Three-dimensional quantitative structure (3D-QSAR) activity relationship studies on ring-substituted quinoline class of anti-tuberculosis agents”. Poster presentation at Molecular Mechanisms of Disease and Drug Action (MMDDA-2005) Conference held during November 16-18, 2005 at Saha Institute of Nuclear Physics, Kolkata, India.

“Electron delocalization in Guanidines”. Poster presentation at 5th National Symposium in Chemistry organized by Chemical Research Society of India (CRSI) held in February 2003 at Chennai, India.

“Computer-aided design of PDE IV inhibitors: Comparative Molecular Field Analysis (CoMFA) of some Thieno[3,2-d]pyrimidine derivatives”. Poster presentation at 54th Indian Pharmaceutical Congress (IPC) held during December 2002 at Pune, India.

Other Conferences

10th International NCCR Symposium in Structural Biology, ETH Zurich, 2-3 Sept 2010, Switzerland

National Symposium on Advances in Magnetic Resonance and its Applications & 12th National Magnetic Resonance Society (NMRS) Meeting during October 8-11, 2005 at Gulmarg, Kashmir and RRL, Jammu, India

XXIst International Conference on Magnetic Resonance in Biological Systems (ICMRBS) organized by Nuclear Magnetic Resonance Society (NMRS) during January 16 –21, 2005 at Hyderabad, India

National Symposium on Cellular and Molecular Biophysics (Indian Biophysics Society); organized by Department of Biophysics, National Institute of Mental Health and Neuro Sciences (NIMHANS) held during January 14-17, 2004 at Bangalore, India

Contact Details

ARC Australian Postdoctoral Fellow
Molecular Dynamics Group
School of Molecular and Microbial Sciences (SMMS)
Molecualr Biosciences building (#76)
The University of Queensland
St. Lucia Campus, Brisbane, QLD 4072
Australia
phone: +61 7 3365 7562
Fax: +61 7 3365 3872
email: a.malde_at_uq.edu.au