Abstract:
:We here report a combined quantum mechanical/molecular mechanical (QM/MM) molecular dynamics (MD) study on the binding interactions between the α(V)β₃ integrin and eight cyclic arginine-glycine-aspartate (RGD) containing peptides. The initial conformation of each peptide within the binding site of the integrin was determined by docking the ligand to the reactive site of the integrin crystal structure with the aid of docking software FRED. The subsequent QM/MM MD simulations of the complex structures show that these eight cyclic RGD-peptides have a generally similar interaction mode with the binding site of the integrin to the cyclo(RGDf-N[M]V) analog found in the crystal structure. Still, there are subtle differences in the interactions of peptide ligands with the integrin, which contribute to the different inhibition activities. The averaged QM/MM protein-ligand interaction energy (IE) is remarkably correlated to the biological activity of the ligand. The IE, as well as a three-variable model which is somewhat interpretable, thus can be used to predict the bioactivity of a new ligand quantitatively, at least within a family of analogs. The present study establishes a helpful protocol for advancing lead compounds to potent inhibitors.
journal_name
J Mol Modeljournal_title
Journal of molecular modelingauthors
Xiang M,Lin Y,He G,Chen L,Yang M,Yang S,Mo Ydoi
10.1007/s00894-012-1487-zsubject
Has Abstractpub_date
2012-11-01 00:00:00pages
4917-27issue
11eissn
1610-2940issn
0948-5023journal_volume
18pub_type
杂志文章abstract::Ergothioneine (2-mercaptohistidine trimethylbetaine) is a very stable natural compound largely present in cells and tissues of plants and mammals. The biological role of ET is still incompletely understood but its antioxidant properties are well assessed experimentally. However, no theoretical study had been performed...
journal_title:Journal of molecular modeling
pub_type: 杂志文章
doi:10.1007/s00894-019-4220-3
更新日期:2019-10-26 00:00:00
abstract::Quantum chemical calculations using density functional theory BP86/def2-TZVPP and ab initio methods at CCSD(T)/def2-TZVPP have been carried for the telluroketones H2A=Te (A = C, Si, Ge). DFT calculations have also been carried out for the ketones H2C=E (E = O, S, Se, Te) and for the complexes NHC → [H2A=Te] → B(C6F5)3...
journal_title:Journal of molecular modeling
pub_type: 杂志文章
doi:10.1007/s00894-014-2433-z
更新日期:2014-10-01 00:00:00
abstract::Understanding the interactions of the cage molecules with a variety of invited molecules is getting very important. But, the hydrogen bonds can also play a crucial role in the interaction phenomenon. In this work, natural population analysis (NPA), chemical shifts, and atom in molecules (AIM) analysis have been used t...
journal_title:Journal of molecular modeling
pub_type: 杂志文章
doi:10.1007/s00894-019-4255-5
更新日期:2019-12-13 00:00:00
abstract::The mechanism and kinetics of 2,2,3,3,3-pentafluoropropanol (CF₃CF₂CH₂OH) reaction with Chlorine atom (Cl) is investigated in this work. Two hydrogen abstraction channels of the title reaction are identified. The geometries of all the stationary points in the potential energy surface are obtained at the BHandHLYP/6-31...
journal_title:Journal of molecular modeling
pub_type: 杂志文章
doi:10.1007/s00894-013-1960-3
更新日期:2013-10-01 00:00:00
abstract::Two uridine 2',3'-cyclic monophosphate (cUMP) derivatives, 5'-deoxy (DcUMP) and 5'-O-methyl (McUMP), were studied by means of quantum chemical methods. Aqueous solvent effects were estimated based on the isodensity-surface polarized-continuum model (IPCM). Gas phase calculations revealed only slight energy differences...
journal_title:Journal of molecular modeling
pub_type: 杂志文章
doi:10.1007/s00894-005-0019-5
更新日期:2006-01-01 00:00:00
abstract::Hydrogen dissociative chemisorption and desorption on small lowest energy Ni(n) clusters up to n=13 as a function of H coverage was studied using density functional theory. H adsorption on the clusters was found to be preferentially at edge sites followed by 3-fold hollow sites and on-top sites. The minimum energy pat...
journal_title:Journal of molecular modeling
pub_type: 杂志文章
doi:10.1007/s00894-011-1059-7
更新日期:2011-09-01 00:00:00
abstract::We have used density-functional theory to investigate the neighboring-group stabilization of iodine, arsenic, and phosphorus-centered oxyanion moieties in species such as deprotonated 2-iodoxybenzoic acid (IBX) and its analogs. The magnitudes of different stabilizing effects and further candidates for analogous stabil...
journal_title:Journal of molecular modeling
pub_type: 杂志文章
doi:10.1007/s00894-009-0567-1
更新日期:2010-03-01 00:00:00
abstract::The performances of quantum chemistry methods (i.e., DFT and ab initio) in calculating the structural and vibrational properties of phosphates and phosphorylated compounds have been evaluated. Diethyl-phosphate, phosphonic acid, dihydrogen phosphate anion, phosphoric acid dimer and protonated glycylphosphotyrosine dip...
journal_title:Journal of molecular modeling
pub_type: 杂志文章
doi:10.1007/s00894-014-2426-y
更新日期:2014-09-01 00:00:00
abstract::Multicenter overlap integrals appearing in the evaluation of multicenter-multielectron integrals of central and noncentral interaction potentials are calculated using complete orthonormal sets of psi(alpha)-ETOs (alpha=1, 0, -1, -2,...). The final results are expressed in terms of two-center overlap integrals between ...
journal_title:Journal of molecular modeling
pub_type: 杂志文章
doi:10.1007/s00894-003-0151-z
更新日期:2003-10-01 00:00:00
abstract::Paracetamol is a relatively safe analgesia/antipyretic drug without the risks of addiction, dependence, tolerance, and withdrawal when used alone. However, when administrated in an opioid/paracetamol combination product, which often contains a large quantity of paracetamol, it can be potentially dangerous due to the r...
journal_title:Journal of molecular modeling
pub_type: 杂志文章
doi:10.1007/s00894-018-3790-9
更新日期:2018-08-18 00:00:00
abstract::CO2 reduction has attracted extensive attentions for its wide applications in chemical engineering and green chemistry. As one of major commercial catalysts, Cu have been widely studied considering its low price and high catalytic efficiency. However, previous studies were mostly focused on the Cu(111) surface, while ...
journal_title:Journal of molecular modeling
pub_type: 杂志文章
doi:10.1007/s00894-020-04448-8
更新日期:2020-07-09 00:00:00
abstract::The mechanism of the thermal rearrangement of substituted N-acyl-2,2-dimethylaziridines 1 has been studied using quantum chemistry methods. Geometries of reactants, transition states and products have been optimized at the B3LYP/6-311++G(2d,2p) level. Relative energies for various stationary points have been determine...
journal_title:Journal of molecular modeling
pub_type: 杂志文章
doi:10.1007/s00894-013-1959-9
更新日期:2013-10-01 00:00:00
abstract::Human gonadotropin hormone receptor, a G-protein coupled receptor, is the target of many medications used in fertility disorders. Obtaining more structural information about the receptor could be useful in many studies related to drug design. In this study, the structure of human gonadotropin receptor was subjected to...
journal_title:Journal of molecular modeling
pub_type: 杂志文章
doi:10.1007/s00894-016-3091-0
更新日期:2016-09-01 00:00:00
abstract::A computational study was carried out to characterize the hydrogen-bonded dimers of Zoledronate (ZOL), which is used widely in treating skeletal diseases. The stable conformations, hydrogen bonding interactions, IR spectra, thermodynamic properties, and electronic characteristics of nine possible ZOL dimers were studi...
journal_title:Journal of molecular modeling
pub_type: 杂志文章
doi:10.1007/s00894-018-3826-1
更新日期:2018-10-09 00:00:00
abstract::Density functional theory and its time-dependent extension (DFT, TDDFT) were employed to establish the feasibility of using a series of 4,4-difluoro-4-bora-3a,4a-diaza-s-indacenes (BODIPYs) in photodynamic therapy. Their absorption electronic spectra, singlet-triplet energy gaps, and spin-orbit matrix elements were co...
journal_title:Journal of molecular modeling
pub_type: 杂志文章
doi:10.1007/s00894-018-3727-3
更新日期:2018-06-29 00:00:00
abstract::The effect of a strong electric field generated by molecular dipoles on the ground state electronic structure and the Q and B states as well as the lowest charge transfer (CT) excited state of porphine-2,5-dimethyl-1,4-benzoquinone (PQ) complex has been investigated theoretically. Density functional theory DFT and tim...
journal_title:Journal of molecular modeling
pub_type: 杂志文章
doi:10.1007/s00894-012-1595-9
更新日期:2013-02-01 00:00:00
abstract::Compound P131 has been established to inhibit Cryptosporidium parvum's inosine monophosphate dehydrogenase (CpIMPDH). Its inhibitory activity supersedes that of paromomycin, which is extensively used in treating cryptosporidiosis. Through the per-residue energy decomposition approach, crucial moieties of P131 were ide...
journal_title:Journal of molecular modeling
pub_type: 杂志文章
doi:10.1007/s00894-020-04663-3
更新日期:2021-01-09 00:00:00
abstract::This work is focused in three topical subjects: intermolecular interactions, metal ions, and aromaticity. A comprehensive MP2/6-31 + G and B3LYP/6-31 + G study of the influence of cation-π interactions on the aromatic character of phosphole was conducted. For this purpose, the structures of complexes were optimized at...
journal_title:Journal of molecular modeling
pub_type: 杂志文章
doi:10.1007/s00894-011-1107-3
更新日期:2012-02-01 00:00:00
abstract::Three-dimensional pharmacophore models of human adenosine receptor A(₂A) antagonists were developed based on 23 diverse compounds selected from a large number of A(₂A) antagonists. The best pharmacophore model, Hypo1, contained five features: one hydrogen bond donor , three hydrophobic points and one ring aromatic. It...
journal_title:Journal of molecular modeling
pub_type: 杂志文章
doi:10.1007/s00894-010-0690-z
更新日期:2010-12-01 00:00:00
abstract::A detailed study of the structural, electronic, and optical absorption properties of crystalline 1,4-dinitrofurazano[3,4-b]piperazine (DNFP) under hydrostatic pressures of 0-100 GPa was performed using periodic density functional theory. As the pressure increases, the lattice constants and cell volumes calculated by L...
journal_title:Journal of molecular modeling
pub_type: 杂志文章
doi:10.1007/s00894-012-1547-4
更新日期:2013-01-01 00:00:00
abstract::Theoretical investigation of Pt(0)-olefin organometallic complexes containing tertiary phosphine ligands was focused on the strength of platinum-olefin electronic interaction. DFT theoretical study of electronic effects in a substantial number of ethylene derivatives was evaluated in terms of the Pt-olefin binding ene...
journal_title:Journal of molecular modeling
pub_type: 杂志文章
doi:10.1007/s00894-007-0222-7
更新日期:2007-09-01 00:00:00
abstract::The nuclear magnetic shieldings of Si, Ge, and Sn in MH(4-n) Y(n) (M = Si, Ge, Sn; Y = F, Cl, Br, I and n = 1-4) molecular systems are highly influenced by the substitution of one or more hydrogens by heavy-halogen atoms. We applied the linear response elimination of small components (LRESC) formalism to calculate tho...
journal_title:Journal of molecular modeling
pub_type: 杂志文章
doi:10.1007/s00894-014-2417-z
更新日期:2014-09-01 00:00:00
abstract::In this work, the effect of the external electric field (EF) on the drug delivery performance of peptide-based metal-organic framework (MPF) for 6-mercaptopurine (6-MP) drug is investigated by means of the molecular dynamics (MD) simulations. It is found that the strength interaction of drug molecule with MPF is decre...
journal_title:Journal of molecular modeling
pub_type: 杂志文章
doi:10.1007/s00894-019-4178-1
更新日期:2019-09-06 00:00:00
abstract::Artificial neural networks (ANNs) have been successfully trained to model and predict the acidity constants (pK(a)) of 128 various phenols with diverse chemical structures using a quantitative structure-activity relationship. An ANN with 6-14-1 architecture was generated using six molecular descriptors that appear in ...
journal_title:Journal of molecular modeling
pub_type: 杂志文章
doi:10.1007/s00894-005-0050-6
更新日期:2006-02-01 00:00:00
abstract::NBO-NJC decomposition of vicinal (3)J HH spin-spin coupling constants into Lewis, delocalization, and repolarization contributions are presented. A deep study allows to assign the main contributions to specific orbitals or electron delocalizations between two orbitals. (3)J HH torsional dependence and the substituent ...
journal_title:Journal of molecular modeling
pub_type: 杂志文章
doi:10.1007/s00894-014-2225-5
更新日期:2014-07-01 00:00:00
abstract::Trocarin belongs to group D of prothrombin activators derived from snake venom of Tropidechis carinatus and is a rich non-hepatic source of Xa, the only known hepatic prothrombin activator. The structural and functional similarity with Xa makes trocarin an interesting target for exploring the structure-functional rela...
journal_title:Journal of molecular modeling
pub_type: 杂志文章
doi:10.1007/s00894-002-0099-4
更新日期:2002-10-01 00:00:00
abstract::The ladder-type polyheterofluorenes were investigated theoretically by using density functional theory (DFT) to reveal their optical and electronic properties for applications in organic optoelectronic devices. The incorporation of heteroatoms (B, Si, Ge, N, P, O, and S) into the ladder-type highly fused polyfluorene ...
journal_title:Journal of molecular modeling
pub_type: 杂志文章
doi:10.1007/s00894-012-1483-3
更新日期:2012-11-01 00:00:00
abstract::We have systematically explored and investigated the geometrical structures, stability, growth pattern, bonding character, and potential energy surface (PES) of the possible isomers of each cluster for planar B(n)P (n = 1 ∼ 7) at the CCSD(T)/6-311+;G(d)//B3LYP/6-311+G(d) level. A large number of planar structures for ...
journal_title:Journal of molecular modeling
pub_type: 杂志文章
doi:10.1007/s00894-010-0801-x
更新日期:2011-05-01 00:00:00
abstract::The formation of selenium species in some biological processes involves the generation of ionic and radical intermediates such as RSe●, RSe-, RSeO●, and RSeO-, among others. We performed a theoretical study of the possible mechanisms for the reaction of the two simplest Se radicals-the hydroselenyl (HSe●) and seleneni...
journal_title:Journal of molecular modeling
pub_type: 杂志文章
doi:10.1007/s00894-017-3535-1
更新日期:2017-12-05 00:00:00
abstract::Abnormal expression of cyclin-dependent kinase 2 (CDK2)/cyclin-E is detected in colorectal, ovarian, breast and prostate cancers. The study of CDK2 with a bound inhibitor revealed CDK2 as a potential therapeutic target for several proliferative diseases. Several highly selective inhibitors of CDK2 are currently underg...
journal_title:Journal of molecular modeling
pub_type: 杂志文章
doi:10.1007/s00894-012-1620-z
更新日期:2013-02-01 00:00:00