68 research outputs found
Airline environmental efficiency measures considering materials balance principles: an application of a network range-adjusted measure with weak-G disposability
<p>In this paper, we focus on assessing airline environmental efficiency with network structure and build a three-stage efficiency production process. Then, we propose a new model, network range-adjusted measure with weak-G disposability, to measure the environmental efficiency of 29 global airlines based on the data from 2008 to 2015. Finally, a second-stage regression analysis is done to explore the important influencing factors. The main findings are as follows: (1) Eva Air is the airline with the highest efficiency among these 29 airlines; (2) Delta is at the bottom of the efficiency ranking among the 29 airlines and this result is in correlation with its old aircraft fleet; (3) the average efficiency change index in 2014 is the highest in the period 2009â2015; (4) only average fleet age has a slightly significant impact on the overall efficiency and Services efficiency.</p
Charging Free Energy Calculations Using the Generalized Solvent Boundary Potential (GSBP) and Periodic Boundary Condition: A Comparative Analysis Using Ion Solvation and Oxidation Free Energy in Proteins
Free energy simulations using a finite sphere boundary
condition rather than a periodic boundary condition (PBC) are attractive
in the study of very large biomolecular systems. To understand the
quantitative impact of various approximations in such simulations,
we compare charging free energies in both solution and protein systems
calculated in a linear response framework with the Generalized Solvent
Boundary Potential (GSBP) and PBC simulations. For simple ions in
solution, we find good agreements between GSBP and PBC charging free
energies, once the relevant correction terms are taken into consideration.
For PBC simulations with the particle-mesh-Ewald for long-range electrostatics,
the contribution (Î<i>G</i><sub>PâM</sub>)
due to the use of a particle rather than molecule based summation
scheme in real space is found to be significant, as pointed out by
HuĚnenberger and co-workers. For GSBP, when the inner region
is close to be charge neutral, the key correction is the overpolarization
of water molecules at the inner/outer dielectric boundary; the magnitude
of the correction (Î<i>G</i><sub>sâpol</sub>), however, is relatively small. For charging (oxidation) free energy
in proteins, the situation is more complex, although good agreement
between GSBP and PBC can still be obtained when care is exercised.
The smooth dielectric boundary approximation inherent to GSBP tends
to make significant errors when the inner region is featured with
a high net charge. However, the error can be corrected with PoissonâBoltzmann
calculations using snapshots from GSBP simulations in a straightforward
and robust manner. Because of the more complex charge and solvent
distributions, the magnitudes of Î<i>G</i><sub>PâM</sub> and Î<i>G</i><sub>sâpol</sub> in protein
simulations appear to be different from those derived for solution
simulations, leading to uncertainty in directly comparing absolute
charging free energies from PBC and GSBP simulations for protein systems.
The relative charging/oxidation free energies, however, are robust.
With the linear response approximation, for the specific protein system
(CueR) studied, the effect of freezing the protein structure in the
outer region is found to be small, unless a very small (8 Ă
)
inner region is used; even in the latter case, the result is substantially
improved when the nearby metal binding loop is allowed to respond
to metal oxidation. The implications of these results to the applicability
of GSBP to complex biomolecules and in ab initio QM/MM simulations
are discussed
Substrate and Transition State Binding in Alkaline Phosphatase Analyzed by Computation of Oxygen Isotope Effects
Enzymes are powerful
catalysts, and a thorough understanding of
the sources of their catalytic power will facilitate many medical
and industrial applications. Here we have studied the catalytic mechanism
of alkaline phosphatase (AP), which is one of the most catalytically
proficient enzymes known. We have used quantum mechanics calculations
and hybrid quantum mechanics/molecular mechanics (QM/MM) simulations
to model a variety of isotope effects relevant to the reaction of
AP. We have calculated equilibrium isotope effects (EIEs), binding
isotope effects (BIEs), and kinetic isotope effects (KIEs) for a range
of phosphate mono- and diester substrates. The results agree well
with experimental values, but the model for the reactionâs
transition state (TS) differs from the original interpretation of
those experiments. Our model indicates that isotope effects on binding
make important contributions to measured KIEs on <i>V</i>/<i>K</i>, which complicated interpretation of the measured
values. Our results provide a detailed interpretation of the measured
isotope effects and make predictions that can test the proposed model.
The model indicates that the substrate is deformed in the ground state
(GS) of the reaction and partially resembles the TS. The highly preorganized
active site preferentially binds conformations that resemble the TS
and not the GS, which induces the substrate to adapt to the enzyme,
rather than the other way aroundî¸as with classic âinduced
fitâ models. The preferential stabilization of the TS over
the GS is what lowers the barrier to the chemical step
Multiple Pathways and Time Scales for Conformational Transitions in apo-Adenylate Kinase
The
open/close transition in adenylate kinase (AK) is regarded
as a representative example for large-scale conformational transition
in proteins, yet its mechanism remains unclear despite numerous experimental
and computational studies. Using extensive (âź50 Îźs) explicit
solvent atomistic simulations and Markov state analysis, we shed new
lights on the mechanism of this transition in the apo form of AK.
The closed basin of apo AK features an open NMP domain while the LID
domain closes and rotates toward it. Therefore, although the computed
structural properties of the closed ensemble are consistent with previously
reported FRET and PRE measurements, our simulations suggest that NMP
closure is likely to follow AMP binding, in contrast to the previous
interpretation of FRET and PRE data that the apo state was able to
sample the fully closed conformation for âligand selectionâ.
The closed state ensemble is found to be kinetically heterogeneous;
multiple pathways and time scales are associated with the open/close
transition, providing new clues to the disparate time scales observed
in different experiments. Besides interdomain interactions, a novel
mutual information analysis identifies specific intradomain interactions
that correlate strongly to transition kinetics, supporting observations
from previous chimera experiments. While our results underscore the
role of internal domain properties in determining the kinetics of
open/close transition in apo AK, no evidence is observed for any significant
degree of local unfolding during the transition. These observations
about AK have general implications to our view of conformational states,
transition pathways, and time scales of conformational changes in
proteins. The key features and time scales of observed transition
pathways are robust and similar from simulations using two popular
fixed charge force fields
Stabilization of Different Types of Transition States in a Single Enzyme Active Site: QM/MM Analysis of Enzymes in the Alkaline Phosphatase Superfamily
The
first step for the hydrolysis of a phosphate monoester (pNPP<sup>2â</sup>) in enzymes of the alkaline phosphatase (AP) superfamily,
R166S AP and wild-type NPP, is studied using QM/MM simulations based
on an approximate density functional theory (SCC-DFTBPR) and a recently
introduced QM/MM interaction Hamiltonian. The calculations suggest
that similar loose transition states are involved in both enzymes,
despite the fact that phosphate monoesters are the cognate substrates
for AP but promiscuous substrates for NPP. The computed loose transition
states are clearly different from the more synchronous ones previously
calculated for diester reactions in the same AP enzymes. Therefore,
our results explicitly support the proposal that AP enzymes are able
to recognize and stabilize different types of transition states in
a single active site. Analysis of the structural features of computed
transition states indicates that the plastic nature of the bimetallic
site plays a minor role in accommodating multiple types of transition
states and that the high degree of solvent accessibility of the AP
active site also contributes to its ability to stabilize diverse transition-state
structures without the need of causing large structural distortions
of the bimetallic motif. The binding mode of the leaving group in
the transition state highlights that vanadate may not always be an
ideal transition state analog for loose phosphoryl transfer transition
states
Implementation of the Solvent Macromolecule Boundary Potential and Application to Model and Realistic Enzyme Systems
The implementation of the solvent macromolecule boundary
potential
(SMBP) by Benighaus and Thiel (<i>J. Chem. Theory Comput.</i> <b>2009</b>, <i>5</i>, 3114) into the program package
CHARMM is presented. The SMBP allows for the efficient calculation
of solvent effects for large macromolecules using irregularly shaped
dielectric boundaries. In contrast to the generalized solvent boundary
potential (GSBP) by Roux et al. (<i>J. Chem. Phys.</i> <b>2001</b>, <i>114</i>, 2924) from which it is derived,
the SMBP is targeted for quantum mechanical/molecular mechanical (QM/MM)
setups using ab initio methods for the QM part. After presenting benchmark
results for simple model systems, applications of the SMBP for the
calculation of geometries, reaction energy barriers, and vibrational
frequencies for an alkaline phosphatase (AP) enzyme are discussed.
Although the effect of the boundary potential on optimized structures
(including the transition state) and vibrational frequencies is relatively
small, the energetics of the phosphoryl transfer catalyzed by AP depend
significantly on the boundary potential. Finally, to emphasize a unique
feature of our implementation, we apply both SMBP and GSBP to the
calculation of the energy barrier for a proton transfer reaction in
a simple model channel, where the effect of an external transmembrane
potential is studied. Due to the dipolar response of the polar environment,
the effective charge displacement estimated based on the effect of
the membrane potential on the proton transfer energetics deviates
from the net charge that passes the membrane
Free Energy Calculations for the Peripheral Binding of Proteins/Peptides to an Anionic Membrane. 1. Implicit Membrane Models
The
binding of peptides and proteins to the surface of complex
lipid membranes is important in many biological processes such as
cell signaling and membrane remodeling. Computational studies can
aid experiments by identifying physical interactions and structural
motifs that determine the binding affinity and specificity. However,
previous studies focused on either qualitative behaviors of protein/membrane
interactions or the binding affinity of small peptides. Motivated
by this observation, we set out to develop computational protocols
for bimolecular binding to charged membranes that are applicable to
both peptides and large proteins. In this work, we explore a method
based on an implicit membrane/solvent model (generalized Born with
a simple switching in combination with the GouyâChapmanâStern
model for a charged interface), which we expect to lead to useful
results when the binding does not implicate significant membrane deformation
and local demixing of lipids. We show that the binding free energy
can be efficiently computed following a thermodynamic cycle similar
to proteinâligand binding calculations, especially when a Bennett
acceptance ratio based protocol is used to consider both the membrane
bound and solution conformational ensembles. Test calculations on
a series of peptides show that our computational approach leads to
binding affinities in encouraging agreement with experimental data,
including for the challenging example of the bringing of flexible
MARCKS-ED peptides to membranes. The calculations highlight that for
a membrane with a significant fraction of anionic lipids, it is essential
to include the effect of ion adsorption using the Stern model, which
significantly modifies the effective surface charge. This implicit
membrane model based computational protocol helps lay the groundwork
for more systematic analysis of protein/peptide binding to membranes
of complex shape and composition
Why Do Arginine and Lysine Organize Lipids Differently? Insights from Coarse-Grained and Atomistic Simulations
An important puzzle in membrane biophysics
is the difference in
the behaviors of lysine (Lys) and arginine (Arg) based peptides at
the membrane. For example, the translocation of poly-Arg is orders
of magnitude faster than that of poly-Lys. Recent experimental work
suggests that much of the difference can be inferred from the phase
behavior of peptide/lipid mixtures. At similar concentrations, mixtures
of phosphatidylethanolamine (PE) and phosphatidylserine (PS) lipids
display different phases in the presence of these polypeptides, with
a bicontinuous phase observed with poly-Arg peptides and an inverted
hexagonal phase observed with poly-Lys peptides. Here we show that
simulations with the coarse-grained (CG) BMW-MARTINI model reproduce
the experimental results. An analysis using atomistic and CG models
reveals that electrostatic and glycerolâpeptide interactions
play a crucial role in determining the phase behavior of peptideâlipid
mixtures, with the difference between Arg and Lys arising from the
stronger interactions of the former with lipid glycerols. In other
words, the multivalent nature of the guanidinium group allows Arg
to simultaneously interact with both phosphate and glycerol groups,
while Lys engages solely with phosphate; this feature of amino acid/lipid
interactions has not been emphasized in previous studies. The Arg
peptides colocalize with PS in regions of high negative Gaussian curvature
and stabilize the bicontinuous phase. Decreasing the strength of either
the electrostatic interactions or the peptideâglycerol interactions
causes the inverted hexagonal phase to become more stable. The results
highlight the utility of CG models for the investigation of phase
behavior but also emphasize the subtlety of the phenomena, with small
changes in specific interactions leading to qualitatively different
phases
Leaving Group Ability Observably Affects Transition State Structure in a Single Enzyme Active Site
A reactionâs transition state
(TS) structure plays a critical
role in determining reactivity and has important implications for
the design of catalysts, drugs, and other applications. Here, we explore
TS structure in the enzyme alkaline phosphatase using hybrid Quantum
Mechanics/Molecular Mechanics simulations. We find that minor perturbations
to the substrate have major effects on TS structure and the way the
enzyme stabilizes the TS. Substrates with good leaving groups (LGs)
have little cleavage of the phosphorusâLG bond at the TS, while
substrates with poor LGs have substantial cleavage of that bond. The
results predict nonlinear free energy relationships for a single rate-determining
step, and substantial differences in kinetic isotope effects for different
substrates; both trends were observed in previous experimental studies,
although the original interpretations differed from the present model.
Moreover, due to different degrees of phosphorusâLG bond cleavage
at the TS for different substrates, the LG is stabilized by different
interactions at the TS: while a poor LG is directly stabilized by
an active site zinc ion, a good LG is mainly stabilized by active
site water molecules. Our results demonstrate the considerable plasticity
of TS structure and stabilization in enzymes. Furthermore, perturbations
to reactivity that probe TS structure experimentally (i.e., substituent
effects) may substantially perturb the TS they aim to probe, and thus
classical experimental approaches such as free energy relations should
be interpreted with care
Conformational Disorder Enhances Electron Transfer Through Alkyl Monolayers: Ferrocene on Conductive Diamond
We
have investigated the electron-transfer kinetics of ferrocene
groups covalently tethered to surfaces of conductive diamond electrodes.
Electrochemical measurements show that the rates are only weakly dependent
on chain length but are strongly dependent on the surface coverage;
these observations are contrary to what is commonly observed for self-assembled
monolayers on gold, pointing to important mechanistic differences
in electron transfer processes on covalently bonded materials. Molecular
dynamics simulations show that dependence on chain length and molecular
density can be readily explained in terms of dynamic crowding effects.
At low coverage, conformational flexibility of surface-tethered alkyl
chains allows the redox-active ferrocene group to dynamically approach
the diamond surface, leading to facile electron transfer for all surface
molecules. As the coverage is increased, steric crowding causes the
average ferrocene-to-surface distance to increase, decreasing the
electron transfer rate. Even at the most dense packings, the mismatch
between the spacing of surface lattice sites and the optimum alkyl
chain density leads to voids and inherent disorder that facilitates
electron transfer. These results are significant in the design and
optimization of electrocatalytically active surfaces on covalently
bonded materials relevant for electro- and photocatalysis
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