Supercomputing and Scientific Data to Accelerate Drug Discovery
Skaggs School of Pharmacy and Pharmaceutical Sciences Chair in Computer-Aided Drug Design
UCSD Center for Drug Discovery Innovation
Computer simulations of the molecules of life are now emerging as powerful tools for the design of new medications for a wide range of diseases, including cancer, heart disease, and Alzheimer’s. My lab is working to accelerate drug discovery by improving the realism, speed and accuracy of these fundamental simulations. We also created BindingDB, the first openly accessible database of medicinal research data, and we continue to expand and improve this resource in order to support drug discovery efforts worldwide.
One current project involves confronting calculations with matched experimental data to rigorously evaluate and improve the accuracy and speed of the simulations. In a parallel effort, we are using simulations to study the structure of water at the surfaces of biomolecules and learning how to take advantage of this structure in the design of new drugs to bind and disable disease-related proteins. We also are collaborating in the design of novel materials and catalysts for applications in energy production and pharmaceuticals. And we are partnering with pharmaceutical companies to make critical datasets available to drive the invention of new methods in computer-aided drug discovery.
A.B. Bioengineering Magna cum Laude, (1981) Harvard College; Ph.D. in Biochemistry and Molecular Biophysics (1988) Columbia University; M.D. (1989) Columbia University College of Physicians and Surgeons.
Awards and Honors:
Detur Prize (1978); John Harvard Scholarship (1978,1979); Tau Beta Pi Engineering Award (1981); Alfred Steiner Award (1987); Associated Medical Schools Award (1987); Louis Gibofsky Memorial Prize (1989); Howard Hughes Medical Institute Physician Research Fellowship (1991-94). Distinguished Lecture in Computational and Mathematical Biology, University of California, Irvine (2014). Endowed Chair in Computer-Aided Drug Design, UC San Diego, 2010- present. 5th Annual Kollman Lectureship, UC San Francisco, 2016
Co-Director UCSD Center for Drug Discovery Innovation 2013-present. Co-Founder, VeraChem LLC (2000-present). Scientific Advisory Board, Dart Neurosciences, 2013-present. Chair, NIH MSFD study section (2007-2008). Co-Organizer, SAMPL3 and SAMPL4 community prediction exercises, 2011, 2013. Organizer, Keystone Symposium on Computer-Aided Drug Design (2010). Vice-Chair, Faculty Senate, University of Maryland Biotechnology Institute (2008-2009). Editorial Advisory Boards: J. Med. Chem., Biopolymers, etc.
- Elucidated statistical thermodynamics of drug action
- Contributed to structure-based development of mutation-resistant HIV-protease inhibitors
- Invented the Mining Minima technology for computer-aided drug design
- Founded BindingDB, a public, web-accessible medicinal chemistry database
- Li A, Gilson MK. (2018) Protein-ligand binding enthalpies from near-millisecond simulations: Analysis of a preorganization paradox. J Chem Phys. 49(7):072311.
- Slochower DR, Gilson MK. (2018) Motor-like Properties of Nonmotor Enzymes. Biophys J 114(9):2174-2179.
- Gaieb Z. et al. (2018) D3R Grand Challenge 2: blind prediction of protein-ligand poses, affinity rankings, and relative binding free energies. J Comput Aided Mol Des. 32(1):1-20.
- Henriksen NM, Gilson MK.(2017) Evaluating Force Field Performance in Thermodynamic Calculations of Cyclodextrin Host-Guest Binding: Water Models, Partial Charges, and Host Force Field Parameters. J Chem Theory Comput. 13(9):4253-4269.
- Balius TE, Fischer M, Stein RM, Adler TB, Nguyen CN, et al (2017). Testing inhomogeneous solvation theory in structure-based ligand discovery. Proc Natl Acad Sci U S A. 114(33):E6839-E6846.
- Heinzelmann G, Henriksen NM, Gilson MK. et al. (2017) Attach-Pull-Release Calculations of Ligand Binding and Conformational Changes on the First BRD4 Bromodomain. J Chem Theory Comput. 13(7):3260-3275.