Nama: Herlan Setiadi

NIM: 20913002
Matakuliah: Pemodelan dan Simulasi
Extending the Treatment o !a"k#one Energeti"s in Protein $or"e $ields :
%imitations o &as'Phase (uantum Me"hani"s in )e*rodu"ing Protein
+onormational ,istri#utions in Mole"ular ,-nami"s Simulations
Discuss
1. What have been done
Computational studies of proteins based on empirical force fields represent a
powerful tool to obtain structure function relationships at an atomic level, and
are central efforts to solve the protein folding problem.
2. Some results
Continued optimization force fields represents an ongoing effort necessitated
by the everincreasing availability of e!perimental and "uantum #echanical
$"#% data on the systems for which the force fields were designed. &n the
case of the C'()##22 protein allatom force field several lines of evidence
motivated the present wor*. During the original optimization of the ,
dihedral parameter the final ad+ustments included systematically altering the
energy of the ,
)
conformation of the alanine dipeptide to avoid biasing the ,
helical conformation in #D simulations, with #bC- used as the model
system.
.. &mportant conclusion
&t is shown that direct use of a highlevel "#based energy surface for the
peptide bac*bone yields generally improved agreement with e!perimental ,
distributions compared to the C'()##22 force field $/able 0%, although
systematic deviations in and in the helical $/able 1% and sheet $/able 2%
regions are evident $3ig. 2%. /herefore, empirical corrections to the grid
correction were underta*en, correcting, to alarge e!tent, the systematic
deviations.
$or"e . $ield Modeling Through (uantum Me"hani"al +al"ulations :
Mole"ular ,-nami"s Simulations o a Nematogeni" Mole"ule in its
+ondensed Phases
Discuss
1. What have been done
Computing the interaction energy of the 0npentylo!y04cyanobiphenyl
$1-C5% dimer at #62 level, for many geometrical arrangements using the
3ragmentation )econstruction #ethod $3)#%. Discrete 3ourier /ransform
$D3/% calculation are performed for a number of geometries of the
monomer.
2. Some results
a. &ntramolecular "uantum #echanically Derived $"#D% 6otential
/he 1-C5 geometry, as obtained by D3/ optimization compares
favorably with the #62 and D3/ calculations recently performed on
a 1-C5 higher homologue, the 2-C5 molecule. /he torsional
energy profile of each fle!ible dihedral $71872% was sampled by
D3/ calculations in the range981:;
<
=1:;
<
> with steps of 11
<
and the
resulting energies. (ll D3/ energies were used together with the
'essian matri! of the e?uilibrium conformation to parameterize the
intramolecular "#D33, yielding a standard deviation of ;.;111
*@Amol.
b. &ntramolecular 6otential
6olarization functions were added in order to improve the ?uality of
the interaction energy. /he Baussian value of e!ponents of the d
$on C,C,-% and p $on '% function were calibrated to minimize the
energy differences and the obtained values are ;..D and ;.01 for
the d and p functions, respectively. /he difference between the two
nearly isoenergetic minima $6D and /S% is strongly decreased and
the error in the 33 configuration reduces from 1 *@Amol to ;..
*@Amol.
c. #olecular Dynamics
/wo different samples of 1E2 1-C5 molecules were prepared in a
orthorhombic lattice as follows. (n antiparallel dimer, with both
molecular long a!es lying on the z laboratory a!is, was replicated 2,
0, and 0 times along the !, y, and z directions, respectively, and
e!panded to a density of ;.1 gAcm
.
. ( first sample, labeled (, was
e?uilibrated at atmospheric pressure for .; ns, increasing the
temperature gradually from 2D; F to .1; F, to yield an
orientationally ordered bul* phase with density 1.;: gAcm
.
and6
2
G;.2. Conversely, the orientational order of system 5 was removed
by heating the e!panded orthorhombic lattice at 0;; F for 1; ns
under atmospheric pressure. /he temperature was progressively
decreased to .2; F in 1; ns of simulation, yielding an isotropic
phase with 6
2
G;.1 and density 1.;. gAcm
.
. 3our runs at different
temperatures, ranging from .2; F to .1; F in steps of 1; F, were
performed at atmospheric pressure starting from the orientationally
ordered system (.
.. &mportant conclusion
Bood agreement was found in most of the investigated properties, thus
validating the accuracy of the proposed model potential, only derived by
?uantum mechanical calculations. /he "#D33 for the nematogenic 1-C5
molecule was created by the +oined use of the 3)# and the @-HCI
program, for its inter and intra molecular part, respectively. With respect
to former applications, the adoption of a specific intramolecular
description and more accurate estimates of the fragment=fragment
interaction pairs, have allowed us to increase the ?uality of the #D
results. &n fact the e!perimental mass density is here overestimated by
only J2K $versusJ2K of previous 1C5 simulations and the transition
temperatures are accurate withinJ1F.