Apichart Linhananta

B.Sc. McGill, M.Sc. Guelph, Ph.D. Guelph

Physics Department, Lakehead University
955 Oliver Road, Thunder Bay, Ontario, Canada
P7B 5E1
Office: CB-4025, Tel:(807) 343 8016, Fax: (807) 346 7853
apichart.linhananta at lakeheadu.ca

Employment History

Associate Professor, Lakehead University (2007-present)
Assistant Professor, Lakehead University (2002-2007)
Postdoctoral Associate, SUNY at Buffalo (2000-2002)
Postdoctoral Fellow, Deakin University, Australia (1998-2000)


Friends and colleagues around the world.
Teaching webpage for the students.

Research Interests

I. Theoretical Study of Proteins and Biological Systems

Since Levinthal's initial inquiry (1968), protein folding has continued to fascinate biologists, chemists and physicists. Simple theoretical models have illuminate generic aspects of folding, but many properties remain mysterious. We've developed an all-atom model, in which the atoms of a protein are reprsented by a chain of bonded hard spheres. The hard spheres interact by discountinuous square-well and hard-spere interactions, as well as by discontinuous dihedral interactions. Hence, the model is structurally realistic, but is still efficient enough to fold small proteins on a personal computer. The model has successfully been applied to examine the cooperativity of folding [6] as well as the folding mechanism of small helical proteins [1-3] and a beta-hairpin motif [4]. Our work on the helical protein has provided unexpected insights to domain swapping [3], a poorly understood form of protein aggregation and a possible cause of protein folding diseases. I plan to further modify the model and apply it to study the folding of a single protein as well as the interaction between proteins. However, the scope of discontinuous models is limitless. It is highly efficient and is applicable to very complex systems. In addition, it is very flexible and can be easily modify to study other systems of biomolecules as well as complex fluids. Future research may involve study of bio-membranes, membrane proteins or protein recognitions.

The Folding and Aggregation of the Ultra-Fast-Folding Mini-Protein Trp-Cage In organisms, newly expressed proteins begin in the unfolded random-coil state. The ability of proteins to rapidly fold from the randm-coil state to their unique native structures is crucial to the health of all living beings. Most proteins fold to the native states within a few milliseconds to a few seconds. The Trp-Cage is one of the fast-folding protein, and can fold to its native state within a few mircoseconds.

The Trp-Cage Protein Unfolded Random Coil State Folded Native State

We have constructed a computer simulation model to understand why the Trp-Cage fold so fast [1]. The results are shown in the movies below:

Fast-Folding Pathway Helix (red segment) forms rapidly, follow by collapse Slow-folding pathway Rapid collapse, follow by the slow formation of helix

In real organisms (in vivo) more than one proteins are present. In some cases, the proteins will still fold to their native stuctures (left movie below). In some cases, they form of aggregates of two or more proteins (oligomers) leading to protein-folding diseases (see right movie below).

                 Solution of folded Trp-Cage                              Protein Aggregates (Oligomers)

My group is now constructing computational models to understand the folding/aggregation of systems of Trp-cage proteins.

II. Free-Energy Functional Theory of Two-Component Lipid Systems

I am working with Mr. Ian MacKay (former M.Sc. student) on this project. This section is UNDER CONSTRUCTION

III. Collisional Energy Transfer (CET) in Systems of Highly-Excited Hydrocarbons Gas

Quasiclassical trajectory simulations have been performed on highly excited hydrocarbons in rare gas bath. Methods employed include commercial computer codes (VENUS) [6,7], hard-sphere models [4,6], and quantum ab-initio methods. Such simulations provide insights on how hydrocarbon fuels obtain the energy to intitiate combustion reactions. Our works are the first to examine the role of torsional rotors in CET. We found that energy exchange between colliding molecules occur, mainly, via the torsional modes. The "heating up" of the torsional rotors lowers the energy barrier to dissociation reactions, increasing the production of highly reactive radical species that are precusors to combustions.

Relevant Publications

  1. Shulin Zhuang, Lingling Bao, Apichart Linhananta, Weiping Liu (2013) Molecular modeling revealed that ligand dissociation from thyroid hormone receptors is affected by receptor heterodimerization Journal of Molecular Graphics and Modelling, 44, 155-160.
  2. A. Linhananta, G. Amadei, T. Miao (2012) Computer simulation study of folding thermodynamics and kinetics of proteins in osmolytes and denaturants Journal of Physics: Conference Series, 341, 012009.
  3. S. Hadizadeh, A. Linhananta, S.S. Plotkin (2011) Improved Measures for the Shape of a Disordered Polymer to Test a Mean-Field Theory of Collapse Macromolecules, 44, 6182-6197.
  4. A. Linhananta, S. Hadizadeh, S.S. Plotkin (2011) An Effective Solvent Theory Connecting the Underlying Mechanisms of Osmolytes and Denaturants for Protein Stability Biophysical J, 100, 459-468 (18 pages of supplementary material).
  5. S. Zhuang, A. Linhananta, H. Li (2010) Phenotypic effects of Ehlers-Danlos syndrome-associated mutation on the FnIII of tenascin-X PROTEIN SCI, 19, 2231-2239 (plus supplementary material).
  6. A. Linhananta, J. Boer, I. MacKay (2005) The Equilibrium properties and folding kinetics of an all-atom Go model of the Trp-cage J CHEM PHYS, 122, 114901 (15 pages).
  7. A. Linhananta, Y. Zhou (2002) The role of sidechain packing and native contact interactions in folding: Discontinuous molecular dynamics folding simulations of an all-atom Go model of Staphylococcal protein A J CHEM PHYS, 117(19), 8983-8985.
  8. A. Linhananta, H. Zhou, Y. Zhou (2002) The dual role of a loop with low loop contact distance in protein folding and domain swapping PROTEIN SCI 11(7), 1695-1701.
  9. Y. Zhou, A. Linhananta (2002) Role of hydrophilic and hydrophobic contacts in folding of the second beta-hairpin fragments of protein G: Molecular dynamics simulation studies of an all-atom model PROTEINS 47(2),154-162.
  10. A. Linhananta, K.F. Lim (2002) Quasiclassical trajectory calculations of collision energy transfer in propane systems: Multiple direct-encounter of hard-sphere model PHYS CHEM CHEM PHYS 4(4), 577-585.
  11. Y. Zhou, A. Linhananta (2002) Thermodynamics of an all-atom off-lattice model of the fragment B of Staphylococcal protein A:Implication for the origin of the cooperativity of protein folding J PHYS CHEM B 106(6), 1481-1485.
  12. A. Linhananta, K.F. Lim (2000) Quasiclassical trajectory calculations of collisional energy transfer in propane systems PHYS CHEM CHEM PHYS 2(7), 1385-1392.
  13. A. Linhananta, K.F. Lim (1999) Quasiclassical trajectory calculations of collisional energy transfer: the methyl internal rotor in ethane PHYS CHEM CHEM PHYS 1(15), 3467-3471.
  14. A. Linhananta, D.E. Sullivan (1998) Mesomophic polymorphism of binary mixtures of water and surfactants PHYS REV E 57(4), 4547-4557.
  15. A. Linhananta, D.E. Sullivan (1991) Phenomenological theory of smectic-A liquid crystals PHYS REV A 44, 8189-8197.