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Pro-3D: Three-Dimensional Protein Analysis Program
Pro3D is a
program developed in our laboratory for molecular modeling, analyzing and
visualizing 3-dimensional protein structure. The program retrieves protein
structures from X-ray crystallographic or NMR data files such as the Brookhaven
Protein Data Bank and displays their 3-D structure in various forms. The
current version can read all PDB.ENT file formats. The program also enables you
to modify the existing structure or to build the desired protein sequence from
the scratch.
Ribonuclease A phe-phe interaction
Download Free Pro-3D Molecular Modeling Program
Download
Pro3D
Visitors since May 21, 1997: 15,122
This
software is available through our web site. To download and unzip, use Winzip with Windows 95 or higher. Five different energy
minimization algorithms are not available to the public at this time.
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Thermodynamic Criteria of Equilibrium in Structural and
Molecular Biology
(postscript)
Additional explanation
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Determination of Temperature-Invariant Enthalpy in Biological
Systems, Cooperative Biochemical Thermodynamic Compensation and Solvent
Ordering. This method is extremely useful in studies on mutant protein
resulting from site-directed mutagenesis
(postscript)
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Fundamentals of Biochemical Thermodynamics
(postscript)
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Molecular Dynamics and Molecular Mechanics Simulations
(Desk-Top Computations in PC) and Three-Dimensional Protein Analysis Program
in PC(Window 95 version). Download Pro3D
(postscript)
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The Planck-Benzinger thermal work function versus the Giauque function
In 1971, Theodor H. Benzinger proposed a thermal work function to take into
account both Boltzman statistical energy effects and
the energies of quantum-mechanical bonds. While the latter are usually not
altered significantly in micromolecular interactions,
it was Benzinger's conjecture that the large-scale
and long-range changes of conformation which accompany protein folding or
assembly might generate significant energy differences due to the cumulative
alteration of their numerous covalent bond structures. It is probably true that
the Giauque function could have been used and would
have been appropriate -- it simply was not. Rather, Benzinger
pursued a separate path, although one which can be related to the work of Giauque and the other chemists.
A new thermodynamic approach: Innate
thermodynamic quantities
In recent years, it has become of increasing
importance to those interested in thermodynamic aspects of structural and
molecular biology to reach a better understanding of the interrelationship of
the innate chemical bond forces and temperature-dependent energy differences in
biological systems.
It has been established in pure and applied
chemistry of simple molecules that reaction energies at room temperature can be
understood in terms of two contributions, one related to energy differences at
0 K and the other associated with integrals of heat capacities data over a range
of temperatures. The necessity of a comparable separation of the interaction
energy terms for biological reactions, however, has not been obvious to most
workers in structural and molecular biology.
In many areas of chemistry, biochemistry and
structural and molecular biology, the temperature dependence of the state of
equilibrium is of major significance. It is well known that the change in
standard Gibbs free energy is related to the equilibrium constant Keq by the relationship DGo= -RTln
Keq where Keq represents
the equilibrium constant. DGo(T) itself (as well as
DGo ) is
dependent on temperature. The total change in
DGo(or
DG) may be
described as containing an "innate" quantity which has an
extrapolated value at absolute zero. At absolute zero K,
DH(zero)=
DGo
(zero) and DAo(zero)=DUo (zero). The residual values of all of these
quantities(note that entropy is excluded) are the same at absolute zero on the
thermodynamic scale, and may be said to describe the innate thermodynamic stabilty of the system. For chemical reactions, the
difference in these quantities between reactants and products, that is
DHo (zero)= DUo (zero)=DAo (zero)=
DGo (zero),
represents the differences in the innate thermodynamic stability between
reactants and products, or the change in stability between reactants and
products as the reaction occurs.
The Giauque function,
DGo(Total) -
DHo (zero)
= - Phi (zero) would be equivalent to the Planck-Benzinger
thermal work function,
DWo = [ DHo(zero) - DGo(Total)], but
has so far proven sterile in terms of its application to biological systems.
The Giauque function
is a very powerful tool for understanding phenomena which occur over a broad
range of temperature. However, neither specialists nor the general scientific
community would normally conceive that biochemical phenomena involve a wide
temperature range. For this and perhaps other reasons, the Giauque
function has received virtually no use in the biochemical community. By
contrast, the equivalent (although independently derived)Planck-Benzinger thermal work function has proven fruitful.
Planck defined Nernst's heat theorem as (phi), G/T = S - H/T .
A proper substitution of the integrated Kirchhoff equation and rearrangement of this expression
gives
DWo = DHo (To ) -
DGo (T)
Delta W represents the
strictly thermal components of any intra- or intermolecular bonding term in a
system, that is energy other than the inherent differewnce
of the O K portion of the interaction energy. Thus,DWo expresses
completely the thermal energy differences of the process involved. Application
of the thermal work function permits the separation of 0 K energy differences
and energy differences associated with heat capacity integrals for a fuller
understanding of reaction energies.
I hope that this
investigation will aid those interested in learning why thermodynamic
quantities in biochemistry (or macromolecular chemistry in general) should
advantageously be separated out into zero K terms (that is the
temperature-invariant enthalpy) and temperature-dependent terms. From this
viewpoint, it is found that certain components of the total change in may be
described as "innate", that is, the quantity has an extrapolated
value even at absolute zero temperature. For a chemical reaction, the
difference in these quantities represents the difference in the innate
thermodynamic stability between reactants and products, or the change in
stability between reactants and products as the reaction occurs.
In the case
of macromolecular interactions on the scale involved in most biological
systems, however, the difference between the heat capacities of product and
reactant may be substantial enough to totally obscure any difference between
the temperature-invariant enthalpy and the heat integrals. Thus the Gibbs-Helmholtz expression cannot be applied to accurately
describe the non-covalent chemical bond forces operating in a biological
system.
The
temperature-invariant enthalpy is a measure of the chemical force that gives
molecules the cohesiveness to form biological structures and represents the
basic energy level of that interaction. The major advantage of this type of
evaluation is the separation of temperature-invariant interactions from those
which are temperature-dependent. Most biochemical interactions can be more
easily understood in this context than via the ordinary Gibbs-Helmholtz approach; for example, solvent interactions, the
effects of solvent additives such as glycerol, sucrose or Hofmeister
anions on protein interactions, site-specific interactions of macromolecules
and distinguishing between denaturation and protein
self-association.
List of papers published: Selective publications on
biological thrmodynamics
I.
Paul W. Chun, Approximation of the Planck-Benzinger
Thermal Work Function in Protein Refolding in Ribonuclease
Systems, Int'l. J. Quantum Chem. Biology Symposium, 15, 247-258 (1988).
II. Chun, P. W.
1991. Manual for computer-aided analysis of biochemical processes with
Florida 1-2-4, University of Florida copyright reserved (Pro-3D).
III. Wou Seok Jou
and Paul W. Chun, Molecular Mechanics of the Formation of Cholic
Acid Micelles, J. Molecular Graphics, 9, 237-240, 243-246, (1991).
IV. Paul W. Chun and
Wou Seok Jou, Molecular Conformation of Ubiquitinated
Structures and the Implications for Regulatory Function, J. Molecular Graphics
10, 7-11, 18-20 (1992)
V. Paul W. Chun, The
Planck-Benzinger Thermal Work Function: Definition of
Temperature-Invariant Enthalpy in Biological Systems, J. Phys. Chem. 98,
6851-6861 (1994)
VI. Paul W. Chun,
The Planck-Benzinger Thermal Work Function: New
Thermodynamic Studies on Ribonuclease A at low pH, J.
Biol. Chem., 270, 13925-13931, (1995).
VII. Paul W. Chun,
The Planck Benzinger-Thermal Work Function:
Thermodynamic Stability of Chymotrypsinogen A and Ribonuclease A in Glycerol, J. Phys. Chem., 100, 7283-7292
(1996).
VIII. Paul W. Chun,
Planck-Benzinger Thermal Work Function: Thermodynamic
Approach to Site-Specific S-protein and S-Peptides Interactions in the Ribonuclease S' Systems, J. Phys. Chem. B, 101, 7835-7843
(1997)
IX. Paul W. Chun,
Application of Planck-Benzinger Relationships to Biology,
Methods in Enzymology, Vol. 295, 227-268 : Energetics of Biological Macromolecules, Part B, Academic
Press (1998).
X. Paul W. Chun,
Uncovering the Innate Thermodynamic Quantities in Protein Unfolding, In press,
Int'l. J. Quantum Chem. 75, 1027-1042, (1999).
XI. Chun, P. W.
1996. New thermodynamic studies on hydrogen bond energy of liquid water,
American Chemical Society, Biophysical Chemistry, poster 283, 212th National
American Chemical Society Meeting, Orlando, FL.
XII. Chun, P. W.
2000. Thermodynamic molecular switch in biological systems: ribonuclease
S' fragment complementation reactions. Biophysical J. 78: 416-429.
XIII. Chun, P.W.
2000. Thermodynamic molecular switch in macromolecular interactions, Cell Biochemistry
and Biophysics, 33, 149-169.
XIV. Chun, P.W.
2000. Thermodynamic molecular switch in biological systems, International
Quantum Chemistry, Sanibel Symposium, 80, 1181-1198.
XV. Chun, P. W.
2001. Thermodynamic switch in Micelles: Colloids and Surfaces, 181, 183-203.
XVI. Chun, P. W.
2001. Thermodynamic molecular switch in sequence-specific hydrophobic
interactions, submitted, Int'l Quantum Quantum
Biology Symposium.
XVII. Chun, P. W.
(2001) The thermodynamic molecular switch in sequence-specific hydrophobic
interactions, Int'l. J. Quantum Chem. 85, 697-712.
XVIII. Chun, P. W.
(2002) Beyond the Planck-Benzinger thermal work
function: New insights into the role of molecular switches in
biology. Per-Olov Lowdin
Memorial Symposium, Int'l. J. Quantum Chem. 87, 323-353.
XVIV. Chun,
P. W. (2002) Misconception arising from a sign discrepancy in thermodynamic
data for Gibbs free energy change profile of ribonuclease
A, Proteins and Peptide Letters 9, 305-313.
XX. Chun, P. W.
(2003) Thermodynamic molecular switch in sequence-specific interactions of dipeptides: Two approaches Compared,
TheScientificWorld Journal.
3, 176-193.
XXI. Chun, P.
W. (2003) A molecular-level thermodynamic switch controls chemical equilibrium
in sequence-specific hydrophobic interaction of 35
dipeptide pairs, Biophysical Journal, 84, 1352-1369.
XXII. Chun, P. W. (2004)
Planck-Benzinger thermal work function in biological systems: Int'l.
J. Quantum Chem. 100, 994-1002.
XXIII. Chun, P. W. (2004) Why does the human
body maintain a constant 37-degree
temperture?: Thermodynamic switch controls chemical equilibrium in biological
systems, submitted to Cell Biochemistry and Biophysics.
List of abstarcts presented in
national scientific meetings, 1995-present
I.
Marc. S. Lewis, K. Sakaguchi, H. Sakamoto, E. Appella, Paul. W. Chun, Thermodynamic analysis of tetramerization domain of human p53, 39th Annual
Biophysical Soc. Mtg,
San Francisco, California. Biophysical J., 68, No.2 Poster 285
(1995).
II. Paul W. Chun,
Thermodynamic Stability of Chymotrypsinogen A, Alpha-cChymotrypsin and Ribonuclease A
in Glycerol, Poster 28, ACS Biological Chemistry, 212th National ACS meeting,
Orlando, Florida, (1996).
III. Paul W. Chun,
Does the accumulation of ubiqutinated PHF signal a
defect in the ubiquitinated-dependent pathway in
these specific neurons. Inviterd speaker: 11th Annual
Pharmaceutical Society Mtg, April,
Iksan, Korea (1996).
IV. Paul W. Chun,
New Thermodynamic Studies on Hydrogen Bonding in The Dimerization
of Carbxylic Acids, Poster 282, ACS Biophysical
Chemistry, 212th National ACS Meeting, Orlando, Florida (1996).
V. Paul W. Chun,
New Thermodynamic Studies on Hydrogen Bond Energy of Liquid Water, Poster 283,
ACS Biophysical Chemistry, 212th National ACS Meeting, Orlando, Florida (1996).
VI.
Paul W. Chun, Thermodynamic Approach to Site-Specific S-Protein and S-peptides
Interactions in the Ribonuclease S' Systems, Poster
M310, 41st Biophysical Society Annual Meeting, May,
New Orleans, Louisiana (1997).
VII.
Paul W. Chun, Thermodynamic Approach to the Unfolding of the Lysozyme Phage T4 Wild type R96 and Temperature-Sensitive
Mutant R96H (Arg -> His). Biophysical Chemistry, 213th National ACS Meeting,
San Francisco, California (1997).
VIII. Paul W. Chun,
Thermodynamic Approach to the Unfolding of Seven Mutant Forms of phage T4 lysozyme, Poster 411, Biophysical Chemistry, 213th National
ACS meeting, San Francisco, California (1997).
VIX. Paul W. Chun,
Molecular Modeling With Pro-3D: Freeware on the Web,
Poster 410, Biophysical Chemistry, 213th National ACS Meeting,
San Francisco, California (1997).
X. Paul W. Chun,
Thermodynamic approach to the unfolding of seven mutant forms of phage T4 lysozyme, Florida Chemical Society Mtg., May, Orlando,
Florida (1998).
XI. Paul W. Chun,
Uncovering the Innate Thermodynamic Quantities in Protein Unfolding, 38th
Sanibel Symposium, St Augustine, Florida (1998)
XII. Paul W. Chun,
A different approach to the thermodynamic of Protein Unfolding: Has this
concept been correctly applied?, ASBMB meeting,
Washington D.C.(1998).
XIII. Paul W. Chun,
Cold denaturation in protein unfolding: Has this
concept been correctly applied? Biophysical society Meeting, Poster SU-Pos 429, February,
Baltimore, Maryland (1999)
XIV. Paul W. Chun,
Uncovering the Innate Thermodynamic Quantities in Protein Unfolding, 39th
Sanibel Quantum Biology Symposium, Poster 12 ,
February, St.
Augustine,
Florida (1999).
XV. Paul W. Chun, A thermodynamic molecular switch in biological systems,
ASBMB Meeting., Poster 324(B-137) May, San Francisco, California (1999).
XVI. Paul W. Chun,
Thermodynamic molecular switch in micellization,
Florida American Chemical Society Meeting., Poster 30, M
XVII. Paul W. Chun,
University of Florida Facing the New Millennium,
Korean Academy of Science and Technology, Annual Meeting. November, (1999).
XVIII. Paul W.
Chun, Thermodynamic molecular switch in macromolecular reactions. 44th Annual Biophysical
Society meetingg. Poster 2502
(B128), Feb, New Orleans (2000).
XIX. Paul W. Chun,
A thermodynamic molecular switch in biological systems: DNA ligase
I - DNA polymerase beta interaction. 218th National American Chemical Society Meeting.,
Poster 372, August, New Orleans (2000).
XX. Paul W. Chun, A thermodynamic molecular switch in biological systems: Ribonuclease S' fragment complementatin
reactions, 40th Sanibel Symposium, February, St. Augustine, FL. (2000).
XXI. Paul W. Chun, A thermodynamic molecular switch in biological system: Ribonuclease S' fragment complementation
reactions.18th International Congress of Biochemistry and Molecular Biology,
Poster 1487, Birmingham, England (2000).
XXII. Paul W. Chun,
A thermodynamic molecular
switch in micelles, 41st Sanibel symposium, Poster 21, St. Augustine,
Florida (2001).
XXIII. Paul W.
Chun, A thermodynamic molecular switch in micelle, Symposium for FAME 2001,
Orlando, Florida (2001).
XXIV. Paul W. Chun,
Thermodynamic molecular switch in sequence-specific hydrophobic interactions:
Two approaches compared, The Miami Nature Biotechnology Winter symposia, The
Genome and Beyond-Genomics and structural biology for medicine, Miami, Florida
(2002).
XXV. Paul W. Chun, Reaction switches in
sequence-specific hydrophobic interactions, National American Chemical Society
and FAME (2002) Meetings, Orlando, Florida (2002).
XXVI. Paul W. Chun, A molecular-level,
thermodynamic switch controls chemical equilibrium in sequence-specific
hydrophobic interaction of 35 dipeptide pairs, poster 1436, Biophysical Society
Meeting, San Antonio, Texas (2003).
XXVII. Paul W. Chun, Thermodynamic
molecular switch controls chemical equilibrium controls chemical equilibrium in
biological systems: Why does the human body maintain a constant 37-degree
temperature?, Poster 25, 43rd Sanibel symposium, St Augstine, Florida (2003).
XXVIII. Paul W. Chun, Why does the human body
maintain a constant 37-degree temperature?, Platform 1788, 48th Biophysical
Society meeting, Baltimore, Maryland (2004).
XXIX. Paul W. Chun, Planck-Benzinger
thermal work function in Biological systems, IUBMB/ASBMB 2004 meeting, Boston
.(2004).
XXX. Paul W. Chun, Why doesa the human
body maintain a constant 37-degree temperature?, Calorimetric Conferance,
Santa Fe, New Maxico (2004).
HIV protease:Molecular
docking
F8-F120 interaction in RNase
A
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