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

• 2006-2010, Postdoc, David Agard lab, University of California, San Francisco, USA
• 2004-2005, 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

12. Deformations induced by domain pulling forces identify key inter-domain interactions that have been conserved in bacterial proteases
    Bosco K. Ho, Brian Kelch, Pinar Erciyas Bailey, Timothy Street, Neema Salimi and David A. Agard
    Submitted.
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]