Simulating Protein Structures, Complexes, And Dynamics

Steinbach, Peter J.

Abstract

We refined our homology model of the human calcium receptor, and a paper analyzing loop-deletion mutants was published. Two additional papers are in press; one includes a homology model of the Saccharomyces cerevisiae homolog of arylalkylamine N-acetyltransferase, and the other involves modeling of the J3-crystallin of the jellyfish lens. Another study that investigates the structure and function of carboxypeptidase E has been submitted for publication. We have also simulated the dynamics of short peptides in solution using Langevin dynamics and a simplified nonbond potential. A manuscript describing this work is in preparation. Also, our study of antibiotic binding to dihydrofolate reductase is ongoing. We modeled the binding mode of substrate 3,4-dihydroxyphenylglycolaldehyde and its derivatives at the active site of aldose reductase (submitted for publication). We have also studied the oxidation mechansim of aldose reductase with trans-naphthalene-1,2 dihydrodiol (in press). Utilizing combined potentials of quantum mechanics and molecular mechanics, we have investigated the catalytic mechansim of chorismate mutase (submitted for pubilcation) and Serotonin N-acetyltransferase (manuscript in preparation).

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: Center for Information Technology (CIT)
• Type: Intramural Research (Z01)
• Project #: 1Z01CT000265-05
• Application #: 6540964
• Study Section: (CMM)
• Support Year: 5
• Fiscal Year: 2001

Institution

• Name: Computer Research and Technology
• Country: United States

Publications

Douglass, Jacqueline; Gunaratne, Ruwan; Bradford, Davis et al. (2012) Identifying protein kinase target preferences using mass spectrometry. Am J Physiol Cell Physiol 303:C715-27

McQueen, Philip G (2010) Population dynamics of a pathogen: the conundrum of vivax malaria. Biophys Rev 2:111-120

Xie, Y-L; Hassan, S A; Qazi, A M et al. (2009) Intramolecular disulfide bonds of the prolactin receptor short form are required for its inhibitory action on the function of the long form of the receptor. Mol Cell Biol 29:2546-55

Zezula, Josef; Singer, Lisa; Przybyl, Anna K et al. (2008) Synthesis and pharmacological effects of the enantiomers of the N-phenethyl analogues of the ortho and para e- and f-oxide-bridged phenylmorphans. Org Biomol Chem 6:2868-83

Lee, Yong-Sok; Pike, Victor W; Hodoscek, Milan (2008) Identification of the transition states in the inversion of 1,4-benzodiazepines with the ab initio replica path method. J Phys Chem A 112:1604-11

Hassan, Sergio A (2008) Morphology of ion clusters in aqueous electrolytes. Phys Rev E Stat Nonlin Soft Matter Phys 77:031501

Pavlicek, Jiri; Coon, Steven L; Ganguly, Surajit et al. (2008) Evidence that proline focuses movement of the floppy loop of arylalkylamine N-acetyltransferase (EC 2.3.1.87). J Biol Chem 283:14552-8

Berkower, Ira; Patel, Chiraag; Ni, Yisheng et al. (2008) Targeted deletion in the beta20-beta21 loop of HIV envelope glycoprotein gp120 exposes the CD4 binding site for antibody binding. Virology 377:330-8

Hassan, Sergio A (2008) Computer simulation of ion cluster speciation in concentrated aqueous solutions at ambient conditions. J Phys Chem B 112:10573-84

Balla, Andras; Tuymetova, Galina; Toth, Balazs et al. (2008) Design of drug-resistant alleles of type-III phosphatidylinositol 4-kinases using mutagenesis and molecular modeling. Biochemistry 47:1599-607