Abstract：
:The drug discovery process typically involves target identification and design of suitable drug molecules against these targets. Despite decades of experimental investigations in the drug discovery domain, about 96% overall failure rate has been recorded in drug development due to the "undruggability" of various identified disease targets, in addition to other challenges. Likewise, the high attrition rate of drug candidates in the drug discovery process has also become an enormous challenge for the pharmaceutical industry. To alleviate this negative outlook, new trends in drug discovery have emerged. By drifting away from experimental research methods, computational tools and big data are becoming valuable in the prediction of biological target druggability and the drug-likeness of potential therapeutic agents. These tools have proven to be useful in saving time and reducing research costs. As with any emerging technique, however, controversial opinions have been presented regarding the validation of predictive computational tools. To address the challenges associated with these varying opinions, this review attempts to highlight the principles of druggability and drug-likeness and their recent advancements in the drug discovery field. Herein, we present the different computational tools and their reliability of predictive analysis in the drug discovery domain. We believe that this report would serve as a comprehensive guide towards computational-oriented drug discovery research. Graphical abstract Highlights of methods for assessing the druggability of biological targets.
journal_name
J Mol Modeljournal_title
Journal of molecular modelingauthors
Agoni C,Olotu FA,Ramharack P,Soliman MEdoi
10.1007/s00894-020-04385-6subject
Has Abstractpub_date
2020-05-08 00:00:00pages
120issue
6eissn
1610-2940issn
0948-5023pii
10.1007/s00894-020-04385-6journal_volume
26pub_type
杂志文章,评审abstract：:The reactivity of the 5-arylidenerhodanine and 5-arylideneisorhodanine derivatives in reactions with dimethyl maleate was computationally studied at the DFT(M06-2X)/6-311+G(d,p) theory level. Eight stereoisomers of the reaction products were considered. The effect of the solvent was taken into account by means of the ...
journal_title：Journal of molecular modeling
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更新日期：2019-06-14 00:00:00
abstract：:Metallo-β-lactamases (MβLs) can hydrolyze and deactivate lactam-containing antibiotics, which are the major mechanism to cause drug resistance in the treatment of bacterial infections. This has become a global concern due to the lack of clinically approved inhibitors so far. SMB-1 from Serratia marcescents is a novel ...
journal_title：Journal of molecular modeling
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更新日期：2020-03-07 00:00:00
abstract：:Studies of the interaction between phenol and intrinsic graphene, as well as phenol and aluminum doped graphene layer are performed using first principles total energy calculations within the periodic density functional theory. A 4x4 periodic structure is used to explore the adsorption of a phenol molecule on the intr...
journal_title：Journal of molecular modeling
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doi：10.1007/s00894-012-1382-7
更新日期：2012-08-01 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：:The geometries, stabilities, and electronic properties of ScBn (n = 1-12) clusters have been systematically investigated by using density functional theory B3LYP method and coupled-cluster theory CCSD(T) method. It is found that the ground state isomers of ScBn have planar or quasi-planar structure when n ≤ 6, which c...
journal_title：Journal of molecular modeling
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doi：10.1007/s00894-013-1860-6
更新日期：2013-08-01 00:00:00
abstract：:Iridium (III) 2-phenylpyridine (ppy) complexes with two suitable monodentate L ligands [Ir(ppy)₂(L)₂]⁺ (ppy = 2-phenylpyridine, py = pyridine, L = 4-pyCN 1, 4-pyCHO 2, 4-pyCl 3, py 4, 4-pyNH₂ 5) were studied by density functional theory (DFT) and time-dependent DFT methods. The influences of ligands L on the electroni...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-012-1462-8
更新日期：2012-10-01 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：:Ab initio calculations were performed to study the quantum chemistry reactions mechanisms among Hg(0), elemental halogen and O3. The geometry of reactions, transition states (TS), intermediates (M) and products were optimized using the MP2 method at the SDD basis function level for Hg, and using 6-311++G (3df, 3pd) fo...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-015-2707-0
更新日期：2015-06-01 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：:Bacterial cytidylate kinase or cytidine monophosphate kinase (CMP kinase) catalyses the phosphoryl transfer from ATP to CMP and dCMP, resulting in the formation nucleoside diphosphates. In eukaryotes, CMP/UMP kinase catalyses the conversion of UMP and CMP to, respectively, UDP and CDP with high efficiency. This work d...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-008-0291-2
更新日期：2008-05-01 00:00:00
abstract：:The dopamine (DAT), serotontin (SERT) and noradrenalin (NET) transporters are molecular targets for different classes of psychotropic drugs. The crystal structure of Aquifex aeolicus LeuT(Aa) was used as a template for molecular modeling of DAT, SERT and NET, and two putative drug binding sites (pocket 1 and 2) in eac...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-009-0478-1
更新日期：2009-10-01 00:00:00
abstract：:Density functional theory (DFT) was used to study the stereochemistry, thermodynamic stability, and spectra of recently synthesized bis-Betti base derivatives of 2,3-dihydroxynaphthalene obtained through multicomponent reactions of 2,3-dihydroxynaphthalene with aminoisoxazole and benzaldehyde derivatives. The stereoch...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-016-2936-x
更新日期：2016-04-01 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 incidence of tuberculosis infections that are resistant to conventional drug therapy has risen steadily in the last decade. Several of the quinolone antibacterials have been examined as inhibitors of M. tuberculosis infection as well as other mycobacterial infections. However, not much has been done to examine spe...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-006-0133-z
更新日期：2007-01-01 00:00:00
abstract：:The crystal structure of the human cystatin C (hCC) dimer revealed that a stable twofold-symmetric dimer was formed via 3D domain swapping. Domain swapping with the need for near-complete unfolding has been proposed as a possible route for amyloid fibril initiation. Thus, the interesting interactions that occur betwee...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-012-1609-7
更新日期：2013-02-01 00:00:00
abstract：:The effect of crystal modifier 2,2',4,4',6,6'-hexanitrostillbene(HNS) on the reinforcement of crystalline 1,3,5-trinitrotoluene (TNT) was investigated by molecular simulation. The intermolecular interactions between HNS and TNT were revealed by quantum chemistry calculations in detail, strong attractive forces were fo...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-014-2461-8
更新日期：2014-10-01 00:00:00
abstract：:First principles calculations have been performed for C60@C180 carbon double-layer endofullerenes with up to: three diatomic radioiodine molecules (131I2), two potassium radio-iodide (K131I), and three sodium radio-iodide (Na131I) inside. The plane-wave pseudopotential (PP) method within the general gradient approxima...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-017-3538-y
更新日期：2017-12-04 00:00:00
abstract：:The hydrogen bonding interactions between noradrenaline (NA) and DMSO were studied with density functional theory (DFT) regarding their geometries, energies, vibrational frequencies, and topological features of the electron density. The quantum theory of atoms in molecules (QTAIM) and the natural bond orbital (NBO) an...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-011-0956-0
更新日期：2011-10-01 00:00:00
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更新日期：2011-04-01 00:00:00
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journal_title：Journal of molecular modeling
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更新日期：2018-10-09 00:00:00
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journal_title：Journal of molecular modeling
pub_type： 杂志文章
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更新日期：2014-08-01 00:00:00
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journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-011-1178-1
更新日期：2012-04-01 00:00:00
abstract：:The CFIm25 subunit of the heterotetrameric cleavage factor Im (CFIm) is a critical factor in the formation of the poly(A) tail at mRNA 3' end, regulating the recruitment of polyadenylation factors, poly(A) site selection, and cleavage/polyadenylation reactions. We previously reported the homologous protein (EhCFIm25) ...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-018-3729-1
更新日期：2018-07-12 00:00:00
abstract：:Ab initio calculations were employed to study the role of ipso carbon hybridization in halogenated compounds RX (R=methyl, phenyl, acetyl, H and X=F, Cl, Br and I) and its interaction with a phosphorus atom, as occurs in the halogen bonded complex type RX⋯PH3. The analysis was performed using ab initio MP2, MP4 and CC...
journal_title：Journal of molecular modeling
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doi：10.1007/s00894-012-1551-8
更新日期：2013-01-01 00:00:00
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journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-013-1964-z
更新日期：2013-10-01 00:00:00
abstract：:Insulin-like growth factor-binding proteins (IGFBPs) control bioactivity and distribution of insulin-like growth factors (IGFs) through high-affinity complex of IGFBP and IGF. To get more insight into the binding interaction of IGF system, the site-directed mutagenesis and force-driving desorption methods were employe...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
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更新日期：2013-12-01 00:00:00
abstract：:The intercalation process and the structure of montmorillonite intercalated with [rhodamine B]+ cations have been investigated using molecular modeling (molecular mechanics and molecular dynamics simulations), X-ray powder diffraction and IR spectroscopy. The structure of the intercalate depends strongly on the concen...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-002-0107-8
更新日期：2003-02-01 00:00:00
abstract：:The potential energy surfaces in gas phase and in aqueous solution for the nitration of benzene, chlorobenzene, and phenol have been elucidated with density functional theory at the M06-2X/6-311G(d,p) level combined with the polarizable continuum solvent model (PCM). Three reaction intermediates have been identified a...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-017-3561-z
更新日期：2017-12-18 00:00:00
abstract：:Acene-thiophenes compounds have been used successfully as active materials in thin-film transistors and photodetectors. This work aims at obtaining an adequate theoretical framework to accurately characterize the optical and electronic properties of two such compounds: NaT2 and NaT3. This is done by comparing the resu...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-017-3241-z
更新日期：2017-02-01 00:00:00
