Jakub Kostal

Faculty Research Scientist
Address: Innovation Hall

Areas of Expertise

Computational Chemistry, Physical Organic Chemistry, Predictive Toxicology, Green Chemistry

2015­-Present: Research Scientist and Adjunct Professor of Chemistry, The George Washington University, Computational Biology Institute

2013­-2014: Guest Researcher, National Institutes of Health, Laboratory of Computational Biology

2011­-2014: Chief Scientist, Sustainability A to Z

Current Research

Our current research focuses on applying computations to solve problems in predictive toxicology and further the field of safer chemical design. Chemicals and materials created through advanced chemistry are the basis of our society and our economy. Yet, with all of the excellent toxicology that has helped us understand and in some cases predict toxicity  associated with industrial chemicals, little progress has been made in answering the fundamental scientific questions that would allow for the design of chemicals with reduced hazard to humans and the environment. The potential threat that commercial chemicals can pose to our society and the environment through unintended biological activity has become  increasingly clear in recent years. Our group focuses on translating the advances made in computational chemistry, and specifically computer­aided drug discovery, to the design of safer chemicals. The goal is to be able to design new (or re­design exisiting) chemicals in such a way that minimizes their biological activity while maintaining desired function. We employ sophisticated modeling techniques, such as quantum and statistical mechanics using free  energy perturbation calculations, to better understand key intermolecular interactions in various  toxicity pathways, such as skin sensitization, mutagenicity, AChE inhibition or oxidative stress.  


Ph.D. Yale University, 2011 (Bill Jorgensen Group, Theoretical and Biophysical Chemistry)
B.A. Middlebury College, 2006 (Chemistry and Biochemistry)


Book Chapters

1. Kostal, J.; Voutchkova, A. M. Rational chemical design for minimal toxicity in Green Chemistry Strategies for Drug Discovery (Eds Peterson, E.; Cue, B.) Wiley­VCH, Weinheim. Expected publication date: 2015.
2. Kostal, J.; Voutchkova, A. M.; Anastas, P. T. Computationally predicted physiochemical property design rules for reduced toxicity in Designing Safer Chemicals, (Eds Boethling, R.; Voutchkova, A.) 2012 Vol. 9, Handbook of Green Chemistry Series. Wiley­VCH, 

Peer­-reviewed journals

1. Machado, J.­H.; Kostal, J. Toward higher quality data: Assessment of Data Reliability for In Vitro Skin Permeation Using Updated Klimisch Scoring Approaches. In preparation.
2. An, N.; Teng, Y.; Machado, J.H.; Voutchkova­Kostal, A. M. Kostal, J. Predicting Skin Permeation Rate from NMR Spectroscopic Data. J. Chem. Inf. Model. 2015, in review.
3. Melnikov, F.; Kostal, J.; Voutchkova, A.; Zimmerman, J. B.; Anastas, P. External Validation of In Silico Tools for Prediction of Acute Aquatic Toxicity. Chem. Res. Toxicol. 2015, in review.
4. Kostal, J.; Voutchkova­Kostal, A.M. CADRE (Computer­Aided Discovery and REdesign): an Interaction­Based Model for the Skin Sensitization Endpoint. Chem. Res. Toxicol. 2015, accepted for publication.
5. Vilseck, J. Z.; Kostal, J. Tirado­Rives, J.; Jorgensen, W. L. Application of a BOSSGaussian Interface for QM/MM Simulations of Henry and Methyl­Transfer reactions. J. Comput. Chem. 2015, 36, 2064­2074
6. Kostal, J.; Voutchkova, A.; Zimmerman, J. B.; Anastas, P. Identifying and Designing Chemicals with Minimal Acute Aquatic Toxicity. Proc. Natl. Acad. Sci. USA Early edition 2014, E­pub March 17, 2014, DOI: 10.1073/pnas.1314991111.
7. Connors, K.; Voutchkova­Kostal, A. M.; Kostal, J.; Anastas, P.; Zimmerman, J.; Brooks, B. Reducing Aquatic Hazards of Industrial Chemicals: Probabilistic Assessment of Sustainable Molecular Design Guidelines. Environ. Toxicol. Chem. 2014, 33, 1894­1902.
8. Kostal, J.; Voutchkova, A. M.; Weeks, B.; Zimmerman, J. B.; Anastas, P. A Free Energy Approach to the Prediction of Olefin and Epoxide Mutagenicity and Carcinogenicity. Chem. Res. Toxicol. 2012, 25, 2780­2787
9. Voutchkova, A.; Kostal, J.; Connors, K.; Brooks, B.; Anastas, P. Zimmerman, J. B. Towards Rational Molecular Design for Reduced Chronic Aquatic Toxicity. Green Chem. 2012, 14, 1001­1008.
10. Kostal, J.; Voutchkova, A. M.; Jorgensen, W. L. Investigation of Solvent Effects on the Rate and Stereoselectivity of the Henry Reaction. Org. Lett. 2012, 14, 260­263.
11. Voutchkova, A. M.; Kostal, J.; Steinfeld, J.; Emerson, J.; Brooks, B.; Anastas, P.; Zimmerman, J. B. Towards Rational Molecular Design: Derivation of Property Guidelines for Reduced Acute Aquatic Toxicity. Green Chem. 2011, 3, 2373­2379. Green Chemistry 
Top 10 Article (August) 
12. Kostal, J.; Jorgensen, W. L. Thorpe­Ingold Acceleration of Oxirane Formation is Mostly a 
Solvent Effect. J. Am. Chem. Soc. 2010, 132, 8766­8773. JACS Select Article