Research home page
Quick link to my current research group's home page
Quick link to my MacKerell-lab-only wiki page
My contact information could be found here
Identifing specific inhibitor for SHP2 protein
Working on identifying specific inhibitors for SHP-2 protein via (CADD) that could bind SHP-2 and inhibit its catalytic activity. This can lead to the development of new drugs that ultimately can serve as treatments of inherited disorder Noonan syndrome and might also contribute to the pathogenesis of some leukemias.
Calulate Potential of Mean Force (PMF) between closed and open states of the SHP2.
WHAM, or Weighted Histogram Analyze Method is used for Free Energy profile calculation.
Developing base derivatives that improve TFO binding to a target duplex
Understanding Mechanisms of DNA adduct formation
Statistical Estimates of the Absolute Internal-Rotational Entropy
See reference 7, 8.
Developing therapies based on Triplex Forming Oligonucleotodes (TFOs)
Spin-labeled DNAs Project was conducted while in graduate school at WVU
See references 4, 5, 6.
Publications & References
11. E. Darian, O. Guvench, B. Yu, C-K. Qu and A. D. MacKerell Jr., “Structural mechanism associated with domain opening in gain-of-function mutations n SHP2 phosphatase.” Proteins: Structure, Function, and Bioinformatics. In press.
10. A. Semenyuk, E. Darian, Liu, Majumdar, Cuenoud, Miller, A. D. MacKerell Jr., M. Seidman. “Targeting of an interrupted polypurine:polypyrimidine sequence in living mammalian cells by a triplex forming oligonucleotide containing a novel base analogue.” Biochemistry, 2010, 49(36), pp 7867-7878.
9. K. Vanommeslaeghe, K., Hatcher, E., Acharya, C., Kundu, S., Zhong, S., Shim, J., Darian, E., Guvench, O., Lopes, P., Vorobyov, I., and MacKerell Jr., A.D. CHARMM General Force Field (CGenFF): A force field for drug-like molecules compatible with the CHARMM all-atom additive biological force fields,” Journal of Computational Chemistry, 31(4), 671-690, 2010.
8. V. Hnizdo, E. Darian, A.Fedorowicz, E. Demchuk, Shengqiao Li, H. Singh. “Nearest-Neighbor Nonparametric Method for Estimating the Configurational Entropy of Complex Molecules”. Journal of Computational Chemistry. 28(3), 655-668 (2006).
7. E. Darian, V. Hnizdo, A. Fedorowicz, H. Singh, E. Demchuk.“Estimation of the Absolute Internal-Rotation Entropy of Molecules with two Torsional Degrees of Freedom from Stochastic Simulations”. Journal of Computational Chemistry. 26(7), 651-660, (2005).
6. E. Darian, P.M. Gannett. “Application of Molecular Dynamics Simulations to spin-labeled Oligonucleotides.” Journal of Biomolecular Structure & Dynamics. 22(5), 579-594, (2005).
5. P.M. Gannett, E. Darian, H. van Tol, N.S. Dalal. “High Field Aqueous EPR of Spin Adducts and Oligonucleotides.” Annual Research Review in Chemistry. Page 12 (2002).
4. P.M. Gannett, E. Darian, J.H. Powell, E.M. Johnson, C.M. Ramsey, N.S. Dalal, and D.E. Budil. “Probing triplex formation by EPR spectroscopy using a newly synthesized spin label for oligonucleotides.” Nucleic Acids Research. 30(23), 5328-5337, (2002).
3. P.M. Gannett, J.H. Powell, E.M. Johnson, E. Darian, N.S. Dalal, M.L. Norton, D.E. Budil. “Solid Phase DNA Annealing Characterization by EPR Spectroscopy.” Tetrahedron letters. 43 (11), 1931-1933, (2002).
2. P.M. Gannett, E. Darian, J.H. Powell, E.M. Johnson. “A Short Procedure for Synthesis of 4-Ethynyl-2,2,6,6-Tetramethyl-3,4-Dehydro-Piperidine-1-Oxyl Nitroxide.” Synthetic Communications. 31 (14), 2137-2141, (2001).
1. P.M. Gannett, J.H. Powell, E. Darian, Y. Zhang, J. Daft, X. Shi, Chem. Res. in Toxicology. “Activation of AP-1 through the MAP Kinase Pathway: A Potential Mechanism of the Carcinogenic Effect of Arenediazonium Ions.” 13 (10), 1020-1027, (2000).
PUBLICATIONS IN PREPARATION
12. “Long-range sequence effect on the arylamine-induced conformational heterogeneity”. V. Jain, E. Darian, S. Patnaik, V. Ganesan, A. D. MacKerell, Jr. and B. Cho ACS-Fall 2010 TOXI