The intercalation process of binding doxorubicin (DOX) in DNA is studied by extensive MD simulations. Many molecular factors that control the binding affinity of DOX to DNA to form a stable complex ...are inspected and quantified by employing continuum solvation models for estimating the binding free energy. The modified MM-PB(GB)SA methodology provides a complete energetic profile of ΔGele, ΔGvDW, ΔGpolar, ΔGnon-polar, TΔStotal, ΔGdeform, ΔGcon, and ΔGion. To identify the sequence specificity of DOX, two different DNA sequences, d(CGATCG) or DNA1 and d(CGTACG) or DNA2, with one molecule (1 : 1 complex) or two molecule (2 : 1 complex) configurations of DOX were selected in this study. Our results show that the DNA deformation energy (ΔGdeform), the energy cost from translational and rotational entropic contributions (TΔStran+rot), the total electrostatic interactions (ΔGpolar-PB/GB + ΔGele) of incorporation, the intramolecular electrostatic interactions (ΔGele) and electrostatic polar solvation interactions (ΔGpolar-PB/GB) are all unfavorable to the binding of DOX to DNA. However, they are overcome by at least five favorable interactions: the van der Waals interactions (ΔGvDW), the non-polar solvation interaction (ΔGnon-polar), the vibrational entropic contribution (TΔSvib), and the standard concentration dependent free energies of DOX (ΔGcon) and the ionic solution (ΔGion). Specifically, the van der Waals interaction appears to be the major driving force to form a stable DOX-DNA complex. We also predict that DOX has stronger binding to DNA1 than DNA2. The DNA deformation penalty and entropy cost in the 2 : 1 complex are less than those in the 1 : 1 complex, thus they indicate that the 2 : 1 complex is more stable than the 1 : 1 complex. We have calculated the total binding free energy (BFE) (ΔGt-sim) using both MM-PBSA and MM-GBSA methods, which suggests a more stable DOX-DNA complex at lower ionic concentration. The calculated BFE from the modified MM-GBSA method for DOX-DNA1 and DOX-DNA2 in the 1 : 1 complex is -9.1 and -5.1 kcal mol-1 respectively. The same quantities from the modified MM-PBSA method are -12.74 and -8.35 kcal mol-1 respectively. The value of the total BFE ΔGt-sim in the 1 : 1 complex is in reasonable agreement with the experimental value of -7.7 ± 0.3 kcal mol-1.
The spike protein of SARS-CoV-2 binds to the ACE2 receptor via its receptor-binding domain (RBD), with the RBD–ACE2 complex presenting an essential molecular target for vaccine development to stall ...the virus infection proliferation. The computational analyses at molecular, amino acid (AA), and atomic levels have been performed systematically to identify the key interacting AAs in the formation of the RBD–ACE2 complex for SARS-CoV and SARS-CoV-2 with its Alpha and Beta variants. Our study uses the molecular dynamics (MD) simulations with the molecular mechanics generalized Born surface area (MM-GBSA) method to predict the binding free energy (BFE) and to determine the actual interacting AAs, as well as two ab initio quantum chemical protocols based on the density functional theory (DFT) implementation. Based on MD results, Q493, Y505, Q498, N501, T500, N487, Y449, F486, K417, Y489, F456, Y495, and L455 have been identified as hotspots in SARS-CoV-2 RBD, while those in ACE2 are K353, K31, D30, D355, H34, D38, Q24, T27, Y83, Y41, and E35. RBD with Alpha and Beta variants has slightly different interacting AAs due to N501Y mutation. Both the electrostatic and hydrophobic interactions are the main driving force to form the AA–AA binding pairs. We confirm that Q493, Q498, N501, F486, K417, and F456 in RBD are the key residues responsible for the tight binding of SARS-CoV-2 with ACE2 compared to SARS-CoV. RBD with the Alpha variant binds with ACE2 stronger than the wild-type RBD or Beta. In the Beta variant, K417N reduces the binding, E484K slightly enhances it, and N501Y significantly increases it as in Alpha. The DFT results reveal that N487, Q493, Y449, T500, G496, G446, and G502 in RBD of SARS2 form pairs via specific hydrogen bonding with Q24, H34, E35, D38, Y41, Q42, and K353 in ACE2.
An effective computational scheme to calculate the complete set of independent elastic constants as well as other structural parameters including bulk modulus, shear modulus, Young's modulus, and ...Poisson's ratio for crystals is reported. The scheme is based on the stress–strain analysis approach with the appropriate selection of strain governed by symmetry consideration. The first principles Vienna ab initio simulation package (VASP) is used in stress calculations. Comprehensive tests were performed for α‐SiO2 and spinel MgAl2O4 with different exchange‐correlation potentials, and different sets of computational parameters to investigate the relative accuracies of the calculations. A wide range of oxides, nitrides, and carbonate crystals with different crystal symmetries were chosen to test the scheme under both LDA and GGA approximations at zero temperature and pressure. Some of these calculations for large complex crystals are believed to be attempted for the first time. The calculated elastic constants show quite good agreement with the existing experimental data for almost all the examined systems with the exception of the relatively soft material such as α‐SiO2 and the C14 parameter of some trigonal crystals expressed in the hexagonal form such as in α‐Al2O3. Other structural properties derived from the elastic constants also show good agreements with the measured values.
Chalcogenide semiconductors and glasses have many applications in the civil and military fields, especially in relation to their electronic, optical and mechanical properties for energy conversion ...and in enviormental materials. However, they are much less systemically studied and their fundamental physical properties for a large class chalcogenide semiconductors are rather scattered and incomplete. Here, we present a detailed study using well defined first-principles calculations on the electronic structure, interatomic bonding, optical, and mechanical properties for 99 bulk chalcogenides including thirteen of these crytals which have never been calculated. Due to their unique composition and structures, these 99 bulk chalcogenides are divided into two main groups. The first group contains 54 quaternary crystals with the structure composition (A
BCQ
) (A = Ag, Cu; B = Zn, Cd, Hg, Mg, Sr, Ba; C = Si, Ge, Sn; Q = S, Se, Te), while the second group contains scattered ternary and quaternary chalcogenide crystals with a more diverse composition (A
B
C
Q
) (A = Ag, Cu, Ba, Cs, Li, Tl, K, Lu, Sr; B = Zn, Cd, Hg, Al, Ga, In, P, As, La, Lu, Pb, Cu, Ag; C = Si, Ge, Sn, As, Sb, Bi, Zr, Hf, Ga, In; Q = S, Se, Te; Formula: see text, 2, 3; Formula: see text, 1, 2, 5; Formula: see text, 1, 2 and Formula: see text, 4, 5, 6, 9). Moreover, the total bond order density (TBOD) is used as a single quantum mechanical metric to characterize the internal cohesion of these crystals enabling us to correlate them with the calculated properties, especially their mechanical properties. This work provides a very large database for bulk chalcogenides crucial for the future theoretical and experimental studies, opening opportunities for study the properties and potential application of a wide variety of chalcogenides.
Abstract
The research of nanocrystalline pyrochlores highlights the importance of the surface structure, composition and segregated point defect in their thermal, electrical, optical, magnetic, and ...catalytic performances. In order to provide a basic view on the surface‐related phenomena, thermodynamic stabilities of three low‐index (100), (110), and (111) surfaces for
A
2
Sn
2
O
7
(
A
= La, Ce, Pr, Nd, Pm, Sm, Eu, or Gd), together with their configurations, electronic structures and related oxygen vacancies are investigated using first‐principles calculations. The (111) surfaces with
A
3
SnO
8
and
A
Sn
3
O
6
terminations are predicted to be stable due to their low surface energies. Meanwhile, the (110) surfaces with
A
2
Sn
2
O
8
and
A
2
Sn
2
O
6
terminations are found to may also form. For these surface structures, the amount of broken bonds play the main role in their structural stability, and the local coordination environment variation also has minor contribution to it. Moreover, oxygen vacancies are observed to segregate on the surface layer, owing to lower energy of breaking bonds accompanying with oxygen vacancy formation and the larger relaxation space comparing to the counterpart in bulk. These results are expected to provide guidance on optimizing the performances of these compounds through surface engineering.
In this study, we report a comprehensive assessment on the elastic and electronic properties of 792 possible MAX (Mn+1AXn) phases with n = 1–4 using ab initio methods. These crystals are then ...screened based on their elastic and thermodynamic stability resulting in a large database of 665 viable crystals. All the experimentally verified MAX phases passed the screening. Various correlations among and between them are fully explored. In particular, the key elements in the interdependence between the elastic properties together with mechanical parameter derived from them and the electronic structure are identified. Detailed analysis of various correlation plots shows that there is a clear correspondence between bulk modulus K and total bond order density (TBOD). Calculations show a marked difference between the carbides and nitrides. This database is also used to test the efficacy of data mining algorithms for materials genome. We further identified several thermodynamically stable new MAX phases with unusual mechanical parameters that have never been synthesized in the laboratory or theoretically investigated. The complete database on the elastic and electronic structure together with the mechanical parameters for these 665 MAX phases compounds are included in the Supplementary Materials and fully accessible.
Silica‐water interaction plays an essential role for the mechanical strength and chemical durability of alkali‐doped‐silicate glasses. A comprehensive study of single and mixed alkali‐silicate ...glasses with 30% molar content of Li2O, Na2O, and K2O, and half‐half mixture of Li2O–Na2O, Li2O–K2O, and Na2O–K2O in hydrated models is carried out using density functional theory methods. Information on atomic geometry, electronic structure, interatomic bonding, partial charge distribution, mechanical, and optical properties are obtained and compared. It confirms that water in the solvated and confined bulk models can be either dissociated or remains as H2O molecule depending on the distribution and specific alkali elements. A quantum mechanical metric, the total bond order density is used to unravel the atomistic origin of the internal cohesion and strength of glasses in different environments. In particular, we show that the mechanical strength of bulk alkali‐silicate glasses is enhanced by hydration with some evidence that mixing of alkali ions tends to degrade the strength of the hydrated glasses. These results are discussed in the context of experimental observations and a few existing simulations using classical molecular dynamics.
The relation between amino acid (AA) sequence and biologically active conformation controls the process of polypeptide chains folding into three-dimensional (3d) protein structures. The recent ...achievements in the resolution achieved in cryo-electron microscopy coupled with improvements in computational methodologies have accelerated the analysis of structures and properties of proteins. However, the detailed interaction between AAs has not been fully elucidated. Herein, we present a
de novo
method to evaluate inter-amino acid interactions based on the concept of accurately evaluating the amino acid bond pairs (AABP). The results obtained enabled the identification of complex 3d long-range interconnected AA interacting network in proteins. The method is applied to the receptor binding domain (RBD) of the SARS-CoV-2 spike protein. We show that although nearest-neighbor AAs in the primary sequence have large AABP, other nonlocal AAs make substantial contribution to AABP with significant participation of both covalent and hydrogen bonding. Detailed analysis of AABP in RBD reveals the pivotal role they play in sequence conservation with profound implications on residue mutations and for therapeutic drug design. This approach could be easily applied to many other proteins of biomedical interest in life sciences.
Gly504 interacting with two nearest neighbor and one non-local amino acids.
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