Abstract：
:A method is suggested to calculate improved entropies within the MM/PBSA approach (molecular mechanics combined with Poisson-Boltzmann and surface area calculations) to estimate protein-ligand binding affinities. In the conventional approach, the protein is truncated outside ~8 A from the ligand. This system is freely minimised using a distance-dependent dielectric constant (to simulate the removed protein and solvent). However, this can lead to extensive changes in the molecular geometry, giving rise to a large standard deviation in this term. In our new approach, we introduce a buffer region approximately 4 A outside the truncated protein (including solvent molecules) and keep it fixed during the minimisation. Thereby, we reduce the standard deviation by a factor of 2-4, ensuring that the entropy term no longer limits the precision of the MM/PBSA predictions. The new method is tested for the binding of seven biotin analogues to avidin, eight amidinobenzyl-indole-carboxamide inhibitors to factor Xa, and two substrates to cytochrome P450 3A4 and 2C9. It is shown that it gives more stable results and often improved predictions of the relative binding affinities.
journal_name
J Comput Aided Mol Desjournal_title
Journal of computer-aided molecular designauthors
Kongsted J,Ryde Udoi
10.1007/s10822-008-9238-zsubject
Has Abstractpub_date
2009-02-01 00:00:00pages
63-71issue
2eissn
0920-654Xissn
1573-4951journal_volume
23pub_type
杂志文章abstract：:Two new computational tools, PRO_PHARMEX and PRO_SCOPE, for use in active-site-directed searching of 3D databases are described. PRO_PHARMEX is a flexible, graphics-based program facilitating the extraction of pharmacophores from the active site of a target macromolecule. These pharmacophores can then be used to searc...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/BF00124472
更新日期：1996-10-01 00:00:00
abstract：:The aspartate protease of the human immune deficiency type-1 virus (HIV-1) has become a crucial antiviral target in which many useful antiretroviral inhibitors have been developed. However, it seems the emergence of new HIV-1 PR mutations enhances drug resistance, hence, the available FDA approved drugs show less acti...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-018-0099-9
更新日期：2018-03-01 00:00:00
abstract：:This paper tests the performance of a simple empirical scoring function on a set of candidate designs produced by a de novo design package. The scoring function calculates approximate ligand-receptor binding affinities given a putative binding geometry. To our knowledge this is the first substantial test of an empiric...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1023/a:1008040323669
更新日期：1998-09-01 00:00:00
abstract：:The recent outbreak of the respiratory syndrome-related coronavirus (SARS-CoV-2) is stimulating an unprecedented scientific campaign to alleviate the burden of the coronavirus disease (COVID-19). One line of research has focused on targeting SARS-CoV-2 proteins fundamental for its replication by repurposing drugs appr...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-020-00356-4
更新日期：2020-10-26 00:00:00
abstract：:The Drug Design Data Resource (D3R) ran Grand Challenge 2015 between September 2015 and February 2016. Two targets served as the framework to test community docking and scoring methods: (1) HSP90, donated by AbbVie and the Community Structure Activity Resource (CSAR), and (2) MAP4K4, donated by Genentech. The challeng...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-016-9946-8
更新日期：2016-09-01 00:00:00
abstract：:New designs for Magnetic Resonance Imaging contrast agents are presented. Essentially, they all are host-guest inclusion complexes between y-cyclodextrins and polyazamacrocycles of gadolinium (III) ion. Substitutions have been made to the host to optimise the host-guest association. Molecular mechanics calculations ha...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1023/a:1027347527385
更新日期：2003-07-01 00:00:00
abstract：:Manifold representations of rotational/translational motion and conformational space of a ligand were previously shown to be effective for local energy optimization. In this paper we report the development of the Monte-Carlo energy minimization approach (MCM), which uses the same manifold representation. The approach ...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-018-0176-0
更新日期：2019-01-01 00:00:00
abstract：:The kinase-regulatory cell signaling networks play a central role in the pathogenesis of human cervical cancer (hCC). However, only few kinase inhibitors have been successfully developed for treatment of this cancer to date. Considering that the active sites of protein kinases are highly conserved and small-molecule i...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-019-00211-1
更新日期：2019-07-01 00:00:00
abstract：:In the recent SAMPL5 challenge, participants submitted predictions for cyclohexane/water distribution coefficients for a set of 53 small molecules. Distribution coefficients (log D) replace the hydration free energies that were a central part of the past five SAMPL challenges. A wide variety of computational methods w...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-016-9954-8
更新日期：2016-11-01 00:00:00
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journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/BF00126219
更新日期：1992-12-01 00:00:00
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journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-018-0126-x
更新日期：2018-07-01 00:00:00
abstract：:Glucokinase (GK) is involved in normal glucose homeostasis and therefore it is a valid target for drug design and discovery efforts. GK activators (GKAs) have excellent potential as treatments of hyperglycemia and diabetes. The combined recent interest in GKAs, together with docking limitations and shortages of dockin...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-014-9740-4
更新日期：2014-05-01 00:00:00
abstract：:A new computer program is described, which positions small molecules into clefts of protein structures (e.g. an active site of an enzyme) in such a way that hydrogen bonds can be formed with the enzyme and hydrophobic pockets are filled with hydrophobic groups. The program works in three steps. First it calculates int...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/BF00124387
更新日期：1992-02-01 00:00:00
abstract：:The one-dimensional model of Hann et al. (JChem Inf Comput Sci 41(3):856–864) has been extended to include reverse binding and wrap-around interaction modes between the protein and ligand to explore the complete combinatorial matrix of molecular recognition. The cumulative distribution function of the Maxwell–Boltzman...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-013-9683-1
更新日期：2013-09-01 00:00:00
abstract：:We present three complementary approaches for score-tuning that improve docking performance in pose prediction, virtual screening and binding affinity assessment. The methodology utilizes experimental data to customize the scoring function for the system of interest considering the specific docking scenario. The tunin...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-011-9482-5
更新日期：2011-11-01 00:00:00
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journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1023/a:1007907728892
更新日期：1997-07-01 00:00:00
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journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1023/a:1008029924865
更新日期：1999-01-01 00:00:00
abstract：:To generate reduced point charge models of proteins, we developed an original approach to hierarchically locate extrema in charge density distribution functions built from the Poisson equation applied to smoothed molecular electrostatic potential (MEP) functions. A charge fitting program was used to assign charge valu...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-011-9471-8
更新日期：2011-10-01 00:00:00
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journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-020-00334-w
更新日期：2020-08-24 00:00:00
abstract：:Virtual Ligand Screening (VLS) has become an integral part of the drug discovery process for many pharmaceutical companies. Ligand similarity searches provide a very powerful method of screening large databases of ligands to identify possible hits. If these hits belong to new chemotypes the method is deemed even more ...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-007-9164-5
更新日期：2008-06-01 00:00:00
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journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-005-9014-2
更新日期：2005-09-01 00:00:00
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journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-014-9823-2
更新日期：2015-05-01 00:00:00
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journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-020-00365-3
更新日期：2021-01-04 00:00:00
abstract：:A three-dimensional quantitative spectrometric data-activity relationship (3D-QSDAR) modeling technique which uses NMR spectral and structural information that is combined in a 3D-connectivity matrix has been developed. A 3D-connectivity matrix was built by displaying all possible assigned carbon NMR chemical shifts, ...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1023/a:1022479510524
更新日期：2002-10-01 00:00:00
abstract：:Dengue and related flaviviruses represent a significant global health threat. The envelope glycoprotein E mediates virus attachment to a host cell and the subsequent fusion of viral and host cell membranes. The fusion process is driven by conformational changes in the E protein and is an essential step in the virus li...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-009-9263-6
更新日期：2009-06-01 00:00:00
abstract：:A major problem in modelling (biological) macromolecules is the search for low-energy conformations. The complexity of a conformational search problem increases exponentially with the number of degrees of freedom which means that a systematic search can only be performed for very small structures. Here we introduce a ...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/BF00129422
更新日期：1992-04-01 00:00:00
abstract：:Bradykinin (BK) is a member of the kinin family, released in response to inflammation, trauma, burns, shock, allergy and some cardiovascular diseases, provoking vasodilatation and increased vascular permeability among other effects. Their actions are mediated through at least two G-protein coupled receptors, B1 a rece...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-015-9890-z
更新日期：2016-01-01 00:00:00
abstract：:Even though it is highly toxic, Amphotericin B (AmB), an amphipathic polyene macrolide antibiotic, is used in the treatment of severe systemic fungal infections as a life-saving drug. To examine the influence of conformational factors on selective toxicity of these compounds, we have investigated the conformational pr...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1023/a:1008144208706
更新日期：2000-10-01 00:00:00
abstract：:Electrostatic potential complementarity between ligands and their receptor sites is evaluated by the superposition of the electrostatic potential, generated by the receptor, onto the ligand potential over the ligand van der Waals surface. We would like to examine which structural factors generate this pattern of super...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/BF00123665
更新日期：1994-10-01 00:00:00
abstract：:During the last few years, we have developed a docking protocol involving two steps: (i) the choice of the most appropriate docking software and parameters for the system of interest using structural and functional information available in public databases (PDB, ChEMBL, PubChem Assay, BindingDB, etc.); (ii) the dockin...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-018-0161-7
更新日期：2019-01-01 00:00:00
