Ruhong Zhou

About me

Ruhong Zhou

Research staff member, IBM Watson

Adjunct Professor, Columbia University


Research lab: Watson Research Center (Yorktown)



Dr. Zhou received his Ph.D. in chemistry from Columbia University (with Prof. Bruce Berne) in 1997. He joined IBM's Thomas J. Watson Research Center in 2000, after spending two and a half years working with Prof. Richard Friesner (Columbia) and Prof. William Jorgensen (Yale) on polarizable force fields and protein-ligand binding mechanisms when he was at Schrodinger. His current research interests include development of novel algorithms for computational biology and bioinformatics, protein folding dynamics, protein-protein interaction, and ligand-receptor binding mechanism. Dr. Zhou is also an Adjunct Professor at Columbia University, Chemistry Department.


Research Interests:
  • Novel Algorithms Development. We have been actively engaged in developing new efficient algorithms for large scale biomolecular simulations. We have recently proposed a Hydrophobic-aided Replica Exchange Method (HAREM) and a Replica Exchange Solute Tempering (REST) method for efficient conformational space sampling. We have previously extended the Fast Multipole Method (FMM) to periodic systems (PFMM); we have also combined the fast algorithms FMM, PFMM, and P3ME for treating long-range electrostatic interactions to an efficient multiple time step algorithm RESPA: FMM/RESPA, PFMM/RESPA, and P3ME/RESPA for molecular dynamics or hybrid Monte Carlo (HMC)simulations; we have also implemented an efficient Poisson-Boltzman solver for continuum solvent, as well as developed a Smart-Walking (S-Walking) method for barrier crossing.

  • Protein Folding Mechanism. Understanding the protein folding mechanism, i.e., how a protein assembles itself quickly (in one second or less) and reliably (repeats the process many many times) has puzzled scientists from many fields for decades. We are currently approaching this problem by large scale molecular dynamics simulations with IBM BlueGene supercomputer. Some of our recent works include the mechanism of single mutation caused protein misfolding, and folding free energy landscapes of small, fast-folding proteins. Various continuum solvent models are also characterized in detail as compared to the experiments and explicit solvent simulations.

  • Nanoscale Dewetting Transition. The nanoscale dewetting transition, although occuring on a microscopic scale, is reminiscent of the first order liquid-vapor phase transition. This nonoscale transition was previously predicted for simple pure hydrophobic plates with statistical theory and computer simulations. Our recent work has shown, however, that this dewetting transition can not only occur in hydrophobic physical systems, such as paraffins, fluorocarbons (teflons), but also in some well-defined biological complexes. More details can be found here.

  • Protein Structure Prediction. Effectively predicting a protein structure from its amino acid sequence is still largely an unsolved problem despite many successful achievements in recent years. We are actively attacking this problem with three different approaches, including homology modeling, fold recognition, and ab initio method. We have developed a new hydrophobic scoring function for detecting native protein folds among large decoy sets, and we are also heavily involved with structure refinement with enhanced sampling techniques, such as Smart Walking Method and various Replica Exchange Methods (REM, HAREM, REST, etc).

  • Ligand-Receptor Binding. The ligand-receptor binding affinity prediction is probably the most challenging problem in structure based rational drug design. We have recently proposed a Linear Interaction Energy method based on a Surface Generalized Born continuum solvent model, LIE-SGB, for binding affinity predictions. The method has been applied to many binding systems, including a 40-ligand binding set, the nevirapine/HEPT analogues binding to HIV-1RT. Very good agreements with experiment have been obtained. We are currently working on further improving the model and applying it to avian flu hemagglutinin (HA) receptor binding as well as antibody binding, together with the more rigorous free energy perturbation (FEP).

Selected Recent Publications
  • J. Li, X. Gong, H. Lu, D. Li, H. Fang and R. Zhou, Electrostatic Gating of a Nanometer Water Channel, Proc. Natl. Acad. Sci., 104, 3687-3692, 2007

  • M. Eleftheriou, R. Germain, A. Royyuru and R. Zhou, Thermal denaturing of mutant lysozyme with both OPLSAA and CHARMM force fields, J. Am. Chem. Soc. 128, 13388-13395, 2006

  • P. Liu, X. Huang, R. Zhou and B. J. Berne, Drying and Hydrophobic Collapse of Melittin Tetramer, Nature, 437, 159-162, 2005

  • R. Zhou, X. Huang, C. Margulius and B. J. Berne, Hydrophobic Collapse in Multi-domain Protein Folding, Science, 305, 1605-1609, 2004

  • R. Zhou, Trp-cage: Folding Free Energy Landscape in Explicit Water, Proc. Natl. Acad. Sci.,100, 13280-13285, 2003

  • R. Zhou, B. J. Berne and R. Germain, Free energy landscape of a beta-hairpin folding in explicit water, Proc. Natl. Acad. Sci. 98, 14931-14936, 2001

  • R. Zhou, R. A. Friesner, A. Ghosh, R. C. Rizzo, and W. L. Jorgensen, New linear interaction method for binding affinity calculations using a continuum solvent model , J. Phys. Chem. B 105, 10388-10397, 2001



Honors and Awards
  • 2005 IBM Outstanding Technical Achievement Award (OTAA), IBM Corporation
  • 2005 IBM Research Division Award, IBM Research
  • 2004 IBM Invention Plateau Award, IBM Corporation
  • 2001 IBM Invention Acheivement Award, IBM Corporation
  • 1997 Columbia University, The Hammett Award
  • 1995 American Chemical Society, DEC Award for Best Graudate Students in Computational Chemistry
  • 1993 Zhejiang University Outstanding Research Award
  • 1993 Second Place Award, Best Science and Technology Projects, China's Ministry of Education
  • 2001-present Adjunct Professor, Columbia University, Department of Chemistry
  • 2003-present Adjunct Professor, Zhejiang University, Institute of Bioinformatics, China
  • 2004-present Guest Professor, Nanjing Univerisity, College of Life Science, China


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Last updated 7 May 2007

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