B.Sc. McGill, M.Sc. Guelph, Ph.D. Guelph
Physics Department, Lakehead University
955 Oliver Road, Thunder Bay, Ontario, Canada
Office: CB-4025, Tel:(807) 343 8016,
Fax: (807) 346 7853
apichart.linhananta at lakeheadu.ca
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.
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 
as well as the folding mechanism of small helical proteins [1-3] and
a beta-hairpin motif . Our work on the helical protein has provided
unexpected insights to domain swapping , 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
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 . The results are shown in the movies below:
Helix (red segment) forms rapidly, follow by collapse
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
III. Collisional Energy Transfer (CET) in Systems of Highly-Excited
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.
- 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.
- 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.
- 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.
- 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).
- 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).
- 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).
- 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.
- 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.
- 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.
- 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.
- 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.
- A. Linhananta, K.F. Lim (2000) Quasiclassical trajectory calculations of
collisional energy transfer in propane systems PHYS CHEM CHEM PHYS
- 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.
- A. Linhananta, D.E. Sullivan (1998) Mesomophic polymorphism of binary
mixtures of water and surfactants PHYS REV E 57(4), 4547-4557.
- A. Linhananta, D.E. Sullivan (1991) Phenomenological theory of
smectic-A liquid crystals
PHYS REV A 44, 8189-8197.