Michael Levitt

Postdoctoral Advisees

Jenelle Bray , Marie Brut , Nir Kalisman , Peter Minary , Avraham Samson , Junjie Zhang

Web Site Links

• Levitt Site

Industry Relationships

Stanford is committed to ethical and transparent interactions with our industry partners. It is our policy to disclose payments of $5,000 or more, equity valued at $5,000 or more in a publicly traded company, or any equity in a privately held company, to physicians and scientists employed by Stanford University from companies or other commercial entities with which they interact as part of their professional activities. View Full Information

Research Interests

Is it possible to understand the molecular structure and function of proteins and nucleic acids in enough detail to make accurate predictions about structure and function? We are mounting a two-pronged attack on this problem using both molecular dynamics simulation and molecular modeling.
(i) Simulation attempts to reproduce the structural, thermodynamic and dynamic properties of a macromolecule in as accurate a way as possible. Starting with simple but realistic expressions for the interactions between atoms and classical laws of motion, we calculate a trajectory that specifies the position and velocity of every atom as a function of time. The time-step between calculated structures is small at 10-15 seconds, and we need to reduce hundreds of thousands of sets of atomic coordinates into a simple coherent description. We have simulated with reasonable fidelity the measurable static and dynamic properties of the several different proteins surrounded by thousands of water molecules. Simulation at different temperatures has allowed exploration of the pathways of protein denaturation of entire proteins and small fragments of protein secondary structure (a-helices and ß-hairpins). Companion studies of DNA double-helix segments in solution preserve the classical double helix while still showing a wide repertoire of interesting motions.
(ii) Molecular modeling attempts to build a model of a macromolecule using known three-dimensional structures and energy minimization as complementary guidelines. Specific examples of this work include the automatic modeling of antibody variable domains, the general modeling of homologous proteins and studies of DNA base-pair mismatches. Questions we are trying to answer include: How can a protein be stabilized by a single amino acid change? How does the sequence of DNA cause local variations of double-helix conformation and stability? Extensive use is made of sophisticated programming, sequence and structural data bases, and computer...

Publications

• Insights into the intra-ring subunit order of tric/cct: a structural and evolutionary analysis. Kalisman N, Levitt M. Pac Symp Biocomput. 2010: 252-9
• Protein segment finder: an online search engine for segment motifs in the PDB. Samson AO, Levitt M. Nucleic Acids Res. 2009; 37 (Database issue): D224-8
• Structural basis of transcription: backtracked RNA polymerase II at 3.4 angstrom resolution. Wang D, Bushnell DA, Huang X, Westover KD, Levitt M, Kornberg RD. Science. 2009; 324 (5931): 1203-6
• Nature of the protein universe. Levitt M, Proc Natl Acad Sci U S A. 2009; 106 (27): 11079-84
• How hydrophobic buckminsterfullerene affects surrounding water structure. Weiss DR, Raschke TM, Levitt M. J Phys Chem B. 2008; 112 (10): 2981-90