Bosco K. Ho

Postdoctoral scholar
David Agard lab
University of California San Francisco

Other stuff of mine.

Contact

• Address: 600 16th Street, Box 2240, San Francisco, CA 94143, USA
  
• Email: bosco@msg.ucsf.edu

Labs I've worked in

• 2006-now, Postdoc, David Agard lab, University of California, San Francisco, USA
• 2003-2005, Postdoc, Dill Group, University of California, San Francisco, USA
• 2002-2003, Postdoc, Centre de Biophysique Moléculaire Numérique, Gembloux, Belgium
• 1997-2001, PhD, Curmi lab, University Of New South Wales, Sydney, Australia
• 1992-1996, BSc, University of New South Wales, Sydney, Australia

Things I Know about Proteins

• Basic elements of protein structure. I have conducted extensive studies into the atomic interactions that determine the basic geometry of the β-sheet; and the Ramachandran plot of the protein backbone in all 20 amino acids, including the tricky cases of glycine, proline and pre-proline. As well, I have identified hitherto ignored rotamers of polar hydrogens in the protein sidechains.
• Perturbative methods in molecular-dynamics simulations. Although molecular dynamics simulations are generally accepted to be a good description of protein dynamics, they are too computer intensive to generate statistically reliable results in simple unbiased simulations. To overcome these limits, I have developed a general local perturbative method that stresses the system artificially in a way that reveals local flexibility in an arbitrary structure. As well, I have developed methods to generate a wide range of large conformational changes.
• Basic algorithms in computational structural biology. My collaborator Vageli Coutsias developed a clean analytical solution of the loop-closure problem that makes use of the 1897 Bricard equation of the flexible tetrahedral angle. I adapted a C version of his code [closure.tar.gz] to help generate a very clean model of the proline sidechain-backbone interaction. One fairly popular library that I have released is a self-contained C library to calculate the RMSD.
• Like every protein theorist and his dog, I have worked on the protein folding problem. In particular, I performed some of the earliest molecular-dynamics simulations of the folding of very short peptides to explore the very earliest stages of nucleation.
• Protein visualization. In my studies of the protein backbone, I found it very difficult to visualize the connection the Ramachandran Plot to the actual 3D conformations of the protein. To facilitate this visualization, I wrote a specialized protein viewer called the Ramachandran Plot Explorer. I have also developed a utility HOLLOW that helps generate clean surfaces of channels, cavities and ligand-binding sites in standard protein viewers. This is a task that has proven to be otherwise next to impossible to do.

Published papers

11. Generating accurate forces in molecular dynamics: the mechanical unfolding of titin, e2lip3 and ubiquitin
    Bosco K. Ho and David A. Agard
    Submitted.
10. Unfolding Simulations Reveal the Mechanism of Extreme Unfolding Cooperativity in the Kinetically Stable α-Lytic Protease (2010)
    Neema L. Salimi, Bosco K. Ho and David A. Agard
    PLOS Computational Biology 6(2):e10000689 [pdf|link]
9. Conserved Tertiary Couplings Stabilize Elements in the PDZ fold, leading to Characteristic Patterns of Domain Conformational Flexibility (2010)
   Bosco K. Ho and David A. Agard
   Protein Science 19:398-411 [pdf|link]
8. Probing the Flexibility of Large Conformational Changes in Protein Structures through Local Perturbations (2009)
   Bosco K. Ho and David A. Agard
   PLOS Computational Biology 5(4): e1000343 [pdf|link]
7. HOLLOW: Generating Accurate Representations of Channel and Interior Surfaces in Molecular Structures (2008)
   Bosco K. Ho and Franz Gruswitz
   BMC Structural Biology 8:49 [pdf|link]
6. Identification of new, well-populated amino-acid sidechain rotamers involving hydroxyl-hydrogen atoms and sulfhydryl-hydrogen atoms (2008)
   Bosco K. Ho and David A Agard
   BMC Structural Biology 8:41 [pdf|link]
5. Folding Very Short Peptides Using Molecular Dynamics (2006)
   Bosco K. Ho and Ken A. Dill
   PLoS Computational Biology 2:e27 [pdf|link]
4. The Ramachandran plots of glycine and pre-proline (2005)
   Bosco K. Ho and Robert Brasseur
   BMC Structural Biology 5:14 [pdf|link]
3. The flexibility in the proline ring couples to the protein backbone (2005)
   Bosco K. Ho, Evangelos A. Coutsias, Chaok Seok and Ken A. Dill
   Protein Science 14:1011 [pdf|pubmed]
2. Revisiting the Ramachandran plot: hard-sphere repulsion, electrostatics, and H-bonding in the α-helix (2003)
   Bosco K. Ho, Annick Thomas and Robert Brasseur
   Protein Science 12:2508 [pdf|pubmed]
1. Twist and shear in β-sheets and β-ribbons (2002)
   Bosco K. Ho, and P. M. G. Curmi
   Journal of Molecular Biology 317:291 [pdf|pubmed]