5 research outputs found
Spectroscopic and Molecular Dynamics Simulation Study of Lysozyme in the Aqueous Mixture of Ethanol: Insights into the Nonmonotonic Change of the Structure of Lysozyme
Structural
change of lysozyme in the aqueous mixture of ethanol
(ETH) has been investigated using emission, circular dichroism spectroscopy,
free-energy molecular dynamics (MD) simulation, and contact map analysis
methods. The emission and circular dichroism data of protein depict
the nonmonotonic change suggesting that the structure as well as local
environment near the Trp of lysozyme modifies differently for different
compositions of the ETH–water mixture. The free-energy MD simulation
shows that the change in the average size of lysozyme in the aqueous
mixture of ETH also shows a nonmonotonic nature. The free-energy profile
of lysozyme in the low concentration of ETH suggests that the distance
between helices increases (χ<sub>ETH</sub> ≈ 0.07) first
and decreases again (χ<sub>ETH</sub> ≈ 0.2) becoming
almost similar to the native structure. Around χ<sub>ETH</sub> ≈ 0.5, the size of lysozyme increases significantly probably
leading to the unfolding of the protein. With further increase of
ETH (χ<sub>ETH</sub> ≈ 0.7), size of lysozyme decreases
suggesting the refolding of the protein. Contact map as well as solvent
organization analysis depicts that ETH gets preferentially solvated
by the hydrophobic core of lysozyme which weaken the hydrophobic interactions
of protein, resulting in the increase in its size. The aggregation
of ETH dominated at the higher concentration of ETH (χ<sub>ETH</sub> ≈ 0.7); hence, the, weakening of hydrophobic core of protein
by ETH is reduced, which probably lead to the refolding of lysozyme
Theoretical Study on the Microhydration of Atmospherically Important Carbonyl Sulfide in Its Neutral and Anionic Forms: Bridging the Gap between the Bulk and Finite Size Microhydrated Cluster
Carbonyl
sulfide (OCS) is the most abundant and stable sulfur-containing
triatomic gas present in the atmosphere that plays an important role
in aerosol formation. Structure, energetics, and photoelectron spectral
properties of the microhydrated OCS in its neutral and anionic forms
have been studied by using the BP86, B3LYP, and MP2 methods. OCS is
linear in the neutral state but bent in the anionic state. Water binds
with the OCS through a single hydrogen bond (O–H···O)
in the OCS-(H<sub>2</sub>O)<sub><i>n</i></sub> [<i>n</i> = 1–6], whereas binding of OCS<sup>–</sup> with water takes place through single as well as double hydrogen
bonds (O–H···S and O–H···O).
Energy decomposition analysis shows that electrostatic and exchange
energies are the main contributors to the stabilization energy of
the microhydrated OCS and OCS<sup>–</sup> clusters. Detachment
as well as solvation energies are calculated with different levels
of theory and compared with the existing experimental values. Finally,
an analytical expression has been used to obtain the bulk value of
the detachment and solvation energies from the existing information
on the finite size clusters. The present study reveals that hydration
increases the detachment energy of the OCS<sup>–</sup> by 3.2
eV. In the absence of experimental bulk values of the detachment and
solvation energies for this system, the values obtained by the solvent-number-dependent
theoretical expression will definitely reduce this gap and may be
used for the modeling of the OCS in the atmosphere
pH Regulates Ligand Binding to an Enzyme Active Site by Modulating Intermediate Populations
Understanding the mechanism of ligands
binding to their
protein
targets and the influence of various factors governing the binding
thermodynamics is essential for rational drug design. The solution
pH is one of the critical factors that can influence ligand binding
to a protein cavity, especially in enzymes whose function is sensitive
to the pH. Using computer simulations, we studied the pH effect on
the binding of a guanidinium ion (Gdm+) to the active site
of hen egg-white lysozyme (HEWL). HEWL serves as a model system for
enzymes with two acidic residues in the active site and ligands with
Gdm+ moieties, which can bind to the active sites of such
enzymes and are present in several approved drugs treating various
disorders. The computed free energy surface (FES) shows that Gdm+ binds to the HEWL active site using two dominant binding
pathways populating multiple intermediates. We show that the residues
close to the active site that can anchor the ligand could play a critical
role in ligand binding. Using a Markov state model, we quantified
the lifetimes and kinetic pathways connecting the different states
in the FES. The protonation and deprotonation of the acidic residues
in the active site in response to the pH change strongly influence
the Gdm+ binding. There is a sharp jump in the ligand-binding
rate constant when the pH approaches the largest pKa of the acidic residue present in the active site. The
simulations reveal that, at most, three Gdm+ can bind at
the active site, with the Gdm+ bound in the cavity of the
active site acting as a scaffold for the other two Gdm+ ions binding. These results can aid in providing greater insights
into designing novel molecules containing Gdm+ moieties
that can have high binding affinities to inhibit the function of enzymes
with acidic residues in their active site
Understanding the Role of Hydrophobic Terminal in the Hydrogen Bond Network of the Aqueous Mixture of 2,2,2-Trifluoroethanol: IR, Molecular Dynamics, Quantum Chemical as Well as Atoms in Molecules Studies
The
aqueous mixture of 2,2,2-trifluoroethanol (TFE) is one of the
important alcoholic solvents which has been extensively used for understanding
the stability of proteins as well as several chemical reactions. In
this paper, the deconvolution of the IR lines in the OH-stretching
region has been applied to understand the local structure of water–water,
alcohol–water, and alcohol–alcohol interactions in the
water mixture of TFE and ethanol (ETH). Further, molecular dynamics
simulations, quantum chemical calculations, and atoms in molecules
analysis have been performed to encode the local structure information
obtained from the experimental data. Addition of a small amount of
alcohol in a pure aqueous medium enhances the aggregation of water
molecules for the case of ETH, whereas the hydrogen bond between TFE
and water is the dominant contributor for TFE. The −CF<sub>3</sub> substitution changes the orientation and hydrogen-bonding
site of water molecules from the hydrophilic OH terminal to the hydrophobic
−CF<sub>3</sub> terminal of TFE, which decreases the clustering
of water molecules as well as enhances the hydrogen bonding between
TFE and water. In the TFE-rich region of the water mixture of TFE,
the fluorine of the TFE molecules interacts with each other through
a weak fluorous interaction which reduces the hydrogen bonding between
the −CF<sub>3</sub> of TFE and water molecules. These findings
about the hydrogen bond network of the water mixture of TFE induced
by the hydrophobic −CF<sub>3</sub> group provide a stepwise
explanation of the unique hydrophobic properties of the trifluoromethyl
group containing pharmaceutical molecules
Role of Dispersive Fluorous Interaction in the Solvation Dynamics of the Perfluoro Group Containing Molecules
Perfluoro
group containing molecules possess an important self-aggregation property
through the fluorous (F···F) interaction which makes
them useful for diverse applications such as medicinal chemistry,
separation techniques, polymer technology, and biology. In this article,
we have investigated the solvation dynamics of coumarin-153 (C153)
and coumarin-6H (C6H) in ethanol (ETH), 2-fluoroethanol (MFE), and
2,2,2-trifluoroethanol (TFE) using the femtosecond upconversion technique
and molecular dynamics (MD) simulation to understand the role of fluorous
interaction between the solute and solvent molecules in the solvation
dynamics of perfluoro group containing molecules. The femtosecond
upconversion data show that the time scales of solvation dynamics
of C6H in ETH, MFE, and TFE are approximately the same whereas the
solvation dynamics of C153 in TFE is slow as compared to that of ETH
and MFE. It has also been observed that the time scale of solvation
dynamics of C6H in ETH and MFE is higher than that of C153 in the
same solvents. MD simulation results show a qualitative agreement
with the experimental data in terms of the time scale of the slow
components of the solvation for all the systems. The experimental
and simulation studies combined lead to the conclusion that the solvation
dynamics of C6H in all solvents as well as C153 in ETH and MFE is
mostly governed by the charge distribution of ester moieties (Cî—»O
and O) of dye molecules whereas the solvation of C153 in TFE is predominantly
due to the dispersive fluorous interaction (F···F)
between the perfluoro groups of the C153 and solvent molecules