Abstract:
:The semiempirical quantum mechanical (SQM) methods used in drug design are commonly parametrized and tested on data sets of systems that may not be representative models for drug-biomolecule interactions in terms of both size and chemical composition. This is addressed here with a new benchmark data set, PLF547, derived from protein-ligand complexes, consisting of complexes of ligands with protein fragments (such as amino-acid side chains), with interaction energies based on MP2-F12 and DLPNO-CCSD(T) calculations. From these, composite benchmark interaction energies are also built for complexes of the ligand with the complete active site of the protein (PLA15 data set). These data sets are used to test multiple SQM methods with corrections for noncovalent interactions; the role of the solvation model in the calculations is tested as well.
journal_name
J Chem Inf Modeljournal_title
Journal of chemical information and modelingauthors
Kříž K,Řezáč Jdoi
10.1021/acs.jcim.9b01171subject
Has Abstractpub_date
2020-03-23 00:00:00pages
1453-1460issue
3eissn
1549-9596issn
1549-960Xjournal_volume
60pub_type
杂志文章abstract::In the preceding paper (Duca, J. S.; Madison, V. S.; Voigt, J. H. J. Chem. Inf. Model. 2008, 48, 659-668), the accuracy of docking and affinity predictions of the Gold and Glide programs were investigated using single protein conformations spanning 150 CDK2/inhibitor crystallographic complexes. High docking accuracy w...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci700428d
更新日期:2008-03-01 00:00:00
abstract::We describe a general methodology for designing an empirical scoring function and provide smina, a version of AutoDock Vina specially optimized to support high-throughput scoring and user-specified custom scoring functions. Using our general method, the unique capabilities of smina, a set of default interaction terms ...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci300604z
更新日期:2013-08-26 00:00:00
abstract::Inhibition of protein-protein interactions (PPIs) is emerging as a promising therapeutic strategy despite the difficulty in targeting such interfaces with drug-like small molecules. PPIs generally feature large and flat binding surfaces as compared to typical drug targets. These features pose a challenge for structura...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.5b00103
更新日期:2015-08-24 00:00:00
abstract::Proteins often have both orthosteric and allosteric binding sites. Endogenous ligands, such as hormones and neurotransmitters, bind to the orthosteric site, while synthetic ligands may bind to orthosteric or allosteric sites, which has become a focal point in drug discovery. Usually, such allosteric modulators bind to...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.0c00695
更新日期:2020-10-26 00:00:00
abstract::The emergence of multidrug-resistant Staphylococcus aureus (S. aureus) makes the treatment of infectious diseases in hospitals more difficult and increases the mortality of the patients. In this study, we attempted to identify novel potent antibiotic candidate compounds against S. aureus dihydrofolate reductase (saDHF...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci400686d
更新日期:2014-04-28 00:00:00
abstract::Halogen bonds (XBs) are attracting increasing attention in biological systems. Protein Data Bank (PDB) archives experimentally determined XBs in biological macromolecules. However, no software for structure refinement in X-ray crystallography takes into account XBs, which might result in the weakening or even vanishin...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.7b00235
更新日期:2017-07-24 00:00:00
abstract::In this study, we aimed to develop a new ligand-based virtual screening approach using an effective shape-overlapping procedure and a more robust scoring function (denoted by the HWZ score for convenience). The HWZ score-based virtual screening approach was tested against the compounds for 40 protein targets available...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci200617d
更新日期:2012-04-23 00:00:00
abstract::The hepatitis C virus (HCV) NS5B RNA-dependent RNA polymerase (RdRP) is a crucial and unique component of the HCV RNA replication machinery and a validated target for drug discovery. Multiple crystal structures of NS5B inhibitor complexes have facilitated the identification of novel compound scaffolds through in silic...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci400644r
更新日期:2014-02-24 00:00:00
abstract::Most physiological effects of thyroid hormones are mediated by the two thyroid hormone receptor subtypes, TRalpha and TRbeta. Several pharmacological effects mediated by TRbeta might be beneficial in important medical conditions such as obesity, hypercholesterolemia and diabetes, and selective TRbeta activation may el...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci900316e
更新日期:2009-11-01 00:00:00
abstract::Human type II topoisomerases, molecular motors that alter the DNA topology, are a major target of modern chemotherapy. Groups of catalytic inhibitors represent a new approach to overcome the known limitations of topoisomerase II poisons such as cardiotoxicity and induction of secondary tumors. Here, we present a class...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.0c00202
更新日期:2020-07-27 00:00:00
abstract::The concept of chemoisosterism of protein environments is introduced as the complementary property to bioisosterism of chemical fragments. In the same way that two chemical fragments are considered bioisosteric if they can bind to the same protein environment, two protein environments will be considered chemoisosteric...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci3002974
更新日期:2013-02-25 00:00:00
abstract::The protection exerted by 3,5-dihydroxy-4-methoxybenzyl alcohol (DHMBA), a phenolic compound recently isolated from the Pacific oyster, against oxidative stress (OS) is investigated using the density functional theory. Our results indicate that DHMBA is an outstanding peroxyl radical scavenger, being about 15 times an...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.5b00513
更新日期:2015-12-28 00:00:00
abstract::Cryo-electron microscopy (cryo-EM) is emerging as a real alternative for structural elucidation. In spite of this, very few cryo-EM structures have been described so far as successful platforms for in silico drug design. Gabapentin and pregabalin are some of the most successful drugs in the treatment of epilepsy and n...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.8b00347
更新日期:2018-08-27 00:00:00
abstract::Our recent studies show that the single Tyr residue in the sequence of amyloid-β42 (Aβ42) is reactive toward various ligands, including metals and adenosine trisphospate (see: Coskuner , O. J. Biol. Inorg. Chem. 2016 , 21 , 957 - 973 and Coskuner , O. ; Murray , I. V. J. J. Alzheimer's Dis. 2014 , 41 , 561 - 574 ). Ho...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.6b00761
更新日期:2017-06-26 00:00:00
abstract::Engineering shape-controlled bionanomaterials requires comprehensive understanding of interactions between biomolecules and inorganic surfaces. We explore the origin of facet-selective binding of peptides adsorbed onto Pt(100) and Pt(111) crystallographic planes. Using molecular dynamics simulations, we show that upon...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci400630d
更新日期:2013-12-23 00:00:00
abstract::A new structure classification scheme for biopolymers is introduced, which is solely based on main-chain dihedral angles. It is shown that by dividing a biopolymer into segments containing two central residues, a local classification can be performed. The method is referred to as DISICL, short for Dihedral-based Segme...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci400541d
更新日期:2014-01-27 00:00:00
abstract::Over the last few decades, anticancer peptides (ACPs) have turned into potential warheads against cancer. Apart from small molecules and monoclonal antibodies, ACPs have been proven to be effective against cancer cells. ACPs are small cationic peptides that selectively bind to the negatively charged cancer cell membra...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.9b00348
更新日期:2020-01-27 00:00:00
abstract::Angiotensin II type 1 receptor (AT1R) is the principal regulator of blood pressure in humans. The overactivation of AT1R by the stimulation of angiotensin II would result in high blood pressure. To prevent hypertension, nonpeptide "sartan" drugs, such as valsartan (VST), have been developed to competitively block the ...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.8b00364
更新日期:2018-10-22 00:00:00
abstract::The determination of the validity of a QSAR model when applied to new compounds is an important concern in the field of QSAR and QSPR modeling. Various scoring techniques can be applied to specific types of models. We present a technique with which we can state whether a new compound will be well predicted by a previo...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci0497511
更新日期:2005-01-01 00:00:00
abstract::The sensitivity of docking calculations to the geometry of the input ligand was studied. It was found that even small changes in the ligand input conformation can lead to large differences in the geometries and scores of the resulting docked poses. The accuracy of docked poses produced from different ligand input stru...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci9000629
更新日期:2009-07-01 00:00:00
abstract::Reduction of the affinity of the fragment crystallizable (Fc) region with immune receptors by substitution of one or a few amino acids, known as Fc-silencing, is an established approach to reduce the immune effector functions of monoclonal antibody therapeutics. This approach to Fc-silencing, however, is problematic a...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.9b01198
更新日期:2020-11-23 00:00:00
abstract::FFAR4 has been considered as a potential target for metabolic diseases, including diabetes. Some compounds with biphenyl scaffold, represented by compound SR13 reported by our group, showed significant FFAR4 selectivity. However, the molecular basis for their selectivity has not been definitely disclosed. This study p...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.9b00735
更新日期:2019-10-28 00:00:00
abstract::We have applied the two most commonly used methods for automatic matched pair identification, obtained the optimum settings, and discovered that the two methods are synergistic. A turbocharging approach to matched pair analysis is advocated in which a first round (a conservative categorical approach that uses an analo...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.7b00335
更新日期:2017-10-23 00:00:00
abstract::A model for prediction of percent intestinal absorption (%Abs) of neutral molecules was developed based upon surface charges of the molecule calculated by density functional theory (DFT). The surface charges are decomposed into sigma moments which are correlated to a partition coefficient representing transfer of the ...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci049653f
更新日期:2005-09-01 00:00:00
abstract::Understanding which physicochemical properties, or property distributions, are favorable for successful design and development of drugs, nutritional supplements, cosmetics, and agrochemicals is of great importance. In this study we have analyzed molecules from three distinct chemical spaces (i) approved drugs, (ii) hu...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci300487z
更新日期:2013-02-25 00:00:00
abstract::The causative agent of African sleeping sickness, Trypanosoma brucei , undergoes an unusual mitochondrial RNA editing process that is essential for its survival. RNA editing terminal uridylyl transferase 2 of T. brucei (TbRET2) is an indispensable component of the editosome machinery that performs this editing. TbR...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci3001327
更新日期:2012-05-25 00:00:00
abstract::New molecular descriptors, RED (Renyi entropy descriptors), based on the generalized entropies introduced by Renyi are presented. Topological descriptors based on molecular features have proven to be useful for describing molecular profiles. Renyi entropy is used as a variability measure to contract a feature-pair dis...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci900275w
更新日期:2009-11-01 00:00:00
abstract::Fragment complementation is gaining an increasing impact as a nonperturbing method to probe noncovalent interactions within protein supersecondary structures. In this study, the fast Fourier transform rigid-body docking algorithm ZDOCK has been employed for in silico reconstitution of the calcium binding protein calbi...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci0501995
更新日期:2005-09-01 00:00:00
abstract::A database has been derived from recently reported [60]fullerene derivatives, and their binding scores with HIV-1 PR have been computed using docking techniques. Computational methods have been used to predict which derivatives may have high binding affinities, and for these compounds biological tests have been perfor...
journal_title:Journal of chemical information and modeling
pub_type: 信件
doi:10.1021/ci900047s
更新日期:2009-05-01 00:00:00
abstract::Characterizing the variability within an ensemble of protein structures is a common requirement in structural biology and bioinformatics. With the increasing number of protein structures becoming available, there is a need for new tools capable of automating the structural comparison of large ensemble of structures. W...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci400233j
更新日期:2013-09-23 00:00:00