Julián Tirado-Rives

Yale University
Department of Chemistry
P. O. Box 208107
New Haven, CT 06520-8107

Voice: (203)432-3356
Fax: (203)432-6144
email: Julian.Tirado-Rives@yale.edu

1977 - Licenciado en Ciencias Químicas (B. Sc. in Chemistry) Instituto Tecnológico y de Estudios Superiores de Monterrey. Monterrey, N. L., México
1985 - Ph. D. in Organic Chemistry Louisiana State University. Baton Rouge, LA, USA
1985 - 1990 Postdoctoral Research Associate in the Laboratories of Prof. William L. Jorgensen, Purdue University. West Lafayette, IN, USA
1990 - 2005 Associate Research Scientist, Yale University, New Haven, CT, USA
2005 - Senior Research Scientist, Yale University, New Haven, CT, USA

Research Interests:

Theoretical approaches to the "Protein Folding" problem:
- Calculations of free energy differences through the use of statistical perturbation theory in Monte Carlo and molecular dynamics simulations of peptides.
- Molecular dynamics simulations of thermally induced unfolding of proteins in solution.
- Effects of chaotropic agents (urea, guanidinium chloride) on the structure of proteins and their unfolding pathway.
Study of mechanisms of enzymatic reactions at the atomic level through statistical mechanics simulations.
Computational methods to study Protein-Ligand Binding and their application to drug design. Protein mutations that confer drug resistance.
Development of Methods and Force Field Parameters for the accurate simulations of organic molecules and biopolymers in Solution.

Selected Publications^*:

Zeevaart, J. G.; Wang, L.; Thakur, V. V.; Leung, C. S.; Tirado-Rives, J.; Bailey, C. M.; Domaoal, R. A.; Anderson, K.S.; Jorgensen, W. L. "Optimization of azoles as anti-human immunodeficiency virus agents guided by free-energy calculations." J. Am. Chem. Soc. 2008, 130, 9492-9499.
Tirado-Rives J.; Jorgensen W. L. "Performance of B3LYP Density Functional Methods for a Large Set of Organic Molecules." J. Chem. Theory Comput. 2008, 4, 297-306.
Kroeger Smith, M. B.; Rader, L. H.; Franklin, A. M.; Taylor, E. V.; Smith, K. D.; Smith, R. H.; Tirado-Rives J.; Jorgensen W. L. "Energetic Effects for Observed and Unobserved HIV-1 Reverse Transcriptase Mutations of Residues L100, V106, and Y181 in the Presence of Nevirapine and Efavirenz." Bioorg. Med. Chem. Lett. 2008, 18, 969-972.
Domaoal, R.A.; McMahon, M.; Thio, C. L.; Bailey, C. M.; Tirado-Rives, J.; Obikhod, A.; Detorio, M.; Rapp, K. L.; Siliciano, R. F.; Schinazi, R. F.; Anderson, K. S. "Pre-steady-state kinetic studies establish entecavir 5'-triphosphate as a substrate for HIV-1 reverse transcriptase." J. Biol. Chem. 2008, 283, 5452-5459.
Barreiro, G.; Guimarães, C. R. W.; Tubert-Brohman, I.; Lyons, T. M.; Tirado-Rives J.; Jorgensen W. L. "Search for Non-Nucleoside Inhibitors of HIV-1 Reverse Transcriptase Using Chemical Similarity, Molecular Docking, and MM-GB/SA Scoring." J. Chem. Inf. Model. 2007, 47, 2416-2428.
Schroeder, S. J.; Blaha, G.; Tirado-Rives, J.; Steitz, T. A.; Moore, P. B. "The Structures of Antibiotics Bound to the E site region of the 50 S Ribosomal Subunit of Haloarcula marismortui: 13-Deoxytedanolide and Girodazole.." J. Mol. Biol. 2007, 367, 1471-1479.
Sattelmeyer, K. W.; Tirado-Rives J.; Jorgensen W. L. "Comparison of SCC-DFTB and NDDO-Based Semiempirical Molecular Orbital Methods for Organic Molecules." J. Phys. Chem. A 2006, 110, 13551-13559.
Tirado-Rives, J.; Jorgensen, W. L. "Contribution of Conformer Focusing on the Uncertainty in Predicting Free Energies for Protein-Ligand Binding." J. Med. Chem. 2006, 49, 5880-5884.
Jorgensen W. L.; Ruiz-Caro J.; Tirado-Rives J.; Basavapathruni A.; Anderson K. S.; Hamilton A. D. "Computer-aided design of non-nucleoside inhibitors of HIV-1 reverse transcriptase." Bioorg Med Chem Lett. 2006, 16, 663-667.
Jorgensen, W. L.; Tirado-Rives, J. "Molecular modeling of organic and biomolecular systems using BOSS and MCPRO." J. Comput. Chem. 2005, 26, 1689-1700.
Jorgensen, W. L.; Tirado-Rives, J. "Potential energy functions for atomic-level simulations of water, and organic and biomolecular systems." Proc. Nat. Acad. Sci. USA 2005, 102, 6656-6670.
Kritzer, J, A.; Hart, S. A.; Qiu, X. J.; Tirado-Rives, J.; Lear, J. D.; Jorgensen, W.L. and Schepartz, A. "Relationship Between Side Chain Structure and 14-helix Stability of β³-Peptides in Water" J. Am. Chem. Soc. 2005, 127, 167-178.
Jorgensen, W. L.; Ulmschneider, J. P.; Tirado-Rives, J. "Free Energies of Hydration from a Generalized Born Model and an All-Atom Force Field." J. Phys. Chem. B 2004, 108, 16264-16270.
Udier-Blagovic, M.; Watkins, E. K.; Tirado-Rives, J. and Jorgensen, W.L. "Structural and Energetic Analysis of the Effects of the K103N Mutation of HIV-1 Reverse Transcriptase on Efavirenz Analogues." J. Med. Chem. 2004, 47, 2389-2392.
Udier-Blagovic, M.; Tirado-Rives, J. and Jorgensen, W. L. "Validation of a Model for the Complex of HIV-1 Reverse Transcriptase with the Novel Non-nucleoside Inhibitor TMC125." J. Am. Chem. Soc. 2003, 125, 6016-6017.
Udier-Blagovic, M.; Watkins, E. K.; Tirado-Rives, J. and Jorgensen, W.L. "Activity Predictions for Efavirenz Analogues with the K103N Mutant of HIV Reverse Transcriptase." Bioorg. Med. Chem. Lett. 2003, 13, 3337-3340.
Guimarães, C.R.W.; Repasky, M.P.; Chandrasekhar, J.; Tirado-Rives, J. and Jorgensen, W.L. "Contributions of Conformational Compression and Preferential Transition State Stabilization to the Rate Enhancement by Chorismate Mutase." J. Am. Chem. Soc. 2003, 125, 6892-6899.
Repasky, M.P.; Guimarães, C.R.W.; Chandrasekhar, J.; Tirado-Rives, J. and Jorgensen, W.L. "Investigation of Solvent Effects for the Claisen Rearrangement of Chorismate to Prephanate: Mechanistic Interpretation via Near Attack Conformations." J. Am. Chem. Soc. 2003, 125, 6663-6672.
Kroeger Smith, M. B.; Hose, B. M.; Hawkins, A.; Lipchock, J.; Farnsworth, D. W.; Rizzo, R. C.; Tirado-Rives, J.; Arnold, E.; Zhang, W.; Hughes, S. H.; Jorgensen, W. L.; Michejda, C. J. and Smith, R. H., Jr. "Molecular Modeling Calculations of HIV-1 Reverse Transcriptase Nonnucleoside Inhibitors: Correlation of Binding Energy with Biological Activity for Novel 2-Aryl-Substituted Benzimidazole Analogs." J. Med. Chem. 2003, 46, 1940-1947.
Rizzo,R. C.; Udier-Blagovic, M.; Wang, D.-P.; Watkins, E. K.; Kroeger Smith, M. B.; Smith, R. H. Jr.; Tirado-Rives, J.; and Jorgensen W. L. "Prediction of Activity for Non-nucleoside Inhibitors with HIV Reverse Transcriptase Based on Monte Carlo Simulations." J. Med. Chem. 2002, 45, 2970-2987.
Wang, D.; Rizzo, R. C.; Tirado-Rives, J. and Jorgensen, W. L. "Antiviral Drug Design: Computational Analyses of the Effects of the L100I Mutation for HIV-RT on the binding of NNRTI's" Bioorg. Med. Chem. Lett, 2001, 11, 2799-2802.
Jorgensen, W. L.; Price, M. L. P.; Price, D. J.; Rizzo, R. C.; Wang, D.;. Pierce, A. C. and Tirado-Rives, J. "COX-2, Src SH2 Domain, HIV Reverse Transcriptase, and Thrombin: Computational Approaches to Drug Design" In Free Energy Calculations in Rational Drug Design, M. R. Reddy and M. D. Elion, Eds., Kluwer, 2001 pp. 299-316.
Kaminski, G.; Friesner, R. A. ; Tirado-Rives, J. and Jorgensen, W. L. "Evaluation and Reparametrization of the OPLS-AA Force Field for Proteins via Comparison with Accurate Quantum Chemical Calculations on Peptides." J. Phys. Chem. B, 2001 , 105, 6474-6487.
Rizzo, R. C.; Tirado-Rives, J. and Jorgensen, W. L. "Estimation of Binding Affinities for HEPT and Nevirapine Analogs with Reverse Transcriptase via Monte Carlo Simulations" J. Med. Chem., 2001, 44, 145-154.
Rizzo, R. C.; Wang, D.; Tirado-Rives, J. and Jorgensen, W. L. "Validation of a Model for the Complex of HIV-1 Reverse Transcriptase with Sustiva through Computation of Resistance Profiles" J. Am. Chem. Soc., 2000, 122, 12898-12900.
Kroeger Smith, M. B.; Lamb, M. L.; Tirado-Rives, J.; Jorgensen, W. L.; Michejda, C. J.; Ruby, S. K. and Smith, R. H. Jr. "Monte Carlo Calculations on HIV-1 Reverse Transcriptase Complexed with the Nonnucleoside Inhibitor 8-Cl TIBO: Contribution of the L100I and Y181C Variants to Protein Stability and Biological Activity" Protein Engin., 2000, 13, 413-421.

* Note: This page does not contain the actual reprints. Instead, the small icons at the end of each reference, if present, are links to the paper in the journal site

using the digital object identifier (doi), and in

pubmed

Some Interesting Links:

At Yale:

Jorgensen Group Home Page
Yale University Department of Chemistry
Yale University

Biological and Computational Resources:

Brookhaven Protein Data Bank WWW Server
EMSL Home Page
BLAST searches at EMBL
BIND (Biomolecular Interaction Network Database)
Brian Shoichet's ZINC Database
Department of Health's AIDSinfo
UCSF HIV InSite
The RNA World website
John Hopkins AIDS service
HIV databases at LANL
AIDS InfoNet
NIH-NIAID DAID
Stanford's HIV drug resistance database
National Library of Medicine HIV/AIDS Informatiom
HIV Resistance Web

Software:

Simulation

Jorgensen Group (BOSS,MCPRO)	AMBER (at Scripps)	CHARMM (Development Project)	GROMOS

GROMACS	NAMD	Tinker

Visualization

Chimera	PyMOL	VMD	MolScript

	RasMol	UCB-Enhanced RasMol (v2.6-ucb)

Search the Chemical Literature:


Chemical Abstracts Service	ISI Web of Knowledge	PubMed	BioMed Central

Journals:



Journal of Chemical Theory and Computation	Journal of Computational Chemistry	Journal of Chemical Information and Modeling

Journal of Molecular Modeling	Journal of Computer-Aided Molecular Design	Biochemistry(ACS)

Bioorganic and Medicinal Chemistry Letters	Journal of Medicinal Chemistry	Journal of Molecular Biology

Journal of Biological Chemistry	Journal of the American Chemical Society	Protein Science

Proceedings of the National Academy of Sciences of the USA	Science	Nature