• DOI:10.1038/87545
• Corpus ID: 6519868

The birth of computational structural biology

@article{Levitt2001TheBO,
  title={The birth of computational structural biology},
  author={Michael Levitt},
  journal={Nature Structural Biology},
  year={2001},
  volume={8},
  pages={392-393}
}

• M. Levitt
• Published 1 May 2001
• Chemistry
• Nature Structural Biology

Like Sydney Altman 1 , I too was initially rejected by the renowned Medical Research Council (MRC) Laboratory of Molecular Biology in Cambridge, England. The year was 1967 and I was then in my final year of a B.Sc. degree in Physics at Kings College in London. Enthralled by John Kendrew's BBC 1964 television series " The Thread of Life " , I wanted desperately to do my Ph.D. at the MRC in Cambridge. Alas there was no room for any new postgraduate students in 1967! After some negotiations, I was accepted for the following year. More importantly, John Kendrew said that I should spend the intervening period at the Weizmann Institute in Israel with Shneior Lifson. Kendrew had just heard of Lifson's initial ideas 2 on the consistent force field (CFF), which was an attempt to simulate the properties of any molecular system from a simple potential energy function. He believed that these methods should be applied to protein and nucleic acid macro-molecules. I arrived in Israel in October, 1967 and set to work programming the consistent force field under the supervision of Lifson and his Ph.D. student Arieh Warshel. At that time, computing at the Weizmann Institute was amongst the best in the world; in 1963 computer engineers there had built their own machine, appropriately known as the Golem, after the Jewish folklore automaton. In a few short months we had a program called CFF that allowed us to calculate the energy, forces (energy first derivatives with respect to atomic positions) and curvature (energy second derivatives with respect to atomic positions) of any molecular system. Warshel went on to use the program to calculate structural, thermodynamic and spectroscopic properties of small organic molecules 3 , while I followed Kendrew's dictum and applied these same programs to proteins. This led to the first energy minimization of an entire protein structure (in fact we did two, myoglobin and lysozyme) in a process that became known as energy refinement 4. I began my Ph.D. at the MRC in Cambridge in September, 1968 and was immediately immersed in the annual tradition of Lab Talks. These talks by members of the three divisions at the Laboratory of Molecular Biology at that time (Structural Studies Division under Kendrew, the Cell Biology Division under Sydney Brenner and Francis Crick, and Protein and Nucleic Acid Chemistry Division under Fred Sanger) were a treat for newcomers to …