Abstract:
:One of the largest commercial applications of enzymes and surfactants is as main components in modern detergents. The high concentration of surfactant compounds usually present in detergents can, however, negatively affect the enzymatic activity. To remedy this drawback, it is of great importance to characterize the interaction between the enzyme and the surfactant molecules at an atomistic resolution. The protein enzyme cutinase from the thermophilic and saprophytic fungus called Humicola insolens (HiC) is a promising candidate for use in detergents thanks to its hydrolase activity targeting mostly biopolyesters (e.g., cutin). HiC is, however, inhibited by low concentrations of sodium dodecyl sulfate (SDS), an ubiquitous surfactant. In this work, we investigate the interaction between HiC and SDS using molecular dynamics simulations. Simulations of HiC dissolved in different aqueous concentrations of SDS show the interaction between HiC and SDS monomers, as well as the formation and dynamics of SDS micelles on the surface of the enzyme. These results suggest a mechanism of cutinase inhibition by SDS, which involves the nucleation of aggregates of SDS molecules on hydrophobic patches on the cutinase surface. Notably, a primary binding site for monomeric SDS is identified near the active site of HiC constituting a possible nucleation point for micelles and leading to the blockage of the entrance to the enzymatic site. Detailed analysis of the simulations allow us to suggest a set of residues from the SDS binding site on HiC to probe as engineered mutations aimed at reducing SDS binding to HiC, thereby decreasing SDS inhibition of HiC.
journal_name
J Chem Inf Modeljournal_title
Journal of chemical information and modelingauthors
Kjølbye LR,Laustsen A,Vestergaard M,Periole X,De Maria L,Svendsen A,Coletta A,Schiøtt Bdoi
10.1021/acs.jcim.8b00857subject
Has Abstractpub_date
2019-05-28 00:00:00pages
1977-1987issue
5eissn
1549-9596issn
1549-960Xjournal_volume
59pub_type
杂志文章abstract::DiSCuS, a "Database System for Compound Selection", has been developed. The primary goal of DiSCuS is to aid researchers in the steps subsequent to generating high-throughput virtual screening (HTVS) results, such as selection of compounds for further study, purchase, or synthesis. To do so, DiSCuS provides (1) a stor...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci400587f
更新日期:2014-01-27 00:00:00
abstract::The emergence of a large amount of pharmacological, genomic, and network knowledge data provides new challenges and opportunities for drug discovery and development. Identification of real small-molecule drug (SM)-miRNA associations is not only important in the development of effective drug repositioning but also cruc...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.0c00244
更新日期:2020-08-24 00:00:00
abstract::Activity cliffs are formed by structurally similar compounds having large potency differences. Coordinated activity cliffs evolve when compounds within groups of structural neighbors form multiple cliffs with different partners, giving rise to local networks of cliffs in a data set. Using particle swarm optimization, ...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci3000503
更新日期:2012-04-23 00:00:00
abstract::In the present contribution, we have developed a database, called the FAR-database, where the acronym FAR stands for Fused Aromatic Rings, which presents the results of nuclear independent chemical shifts calculations, NICS(0), NICS(1), NICS(0)ZZ, and NICS(1)ZZ, of 660 neutral benzenoid-PAHs and cyclopenta-fused PAHs....
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.9b00909
更新日期:2020-02-24 00:00:00
abstract::Computer programs for structure diagram generation (SDG) are indispensable cheminformatic tools that translate one- or three-dimensional (1D or 3D) chemical structure data stored in electronic formats to human-readable 2D depictions. Although many such programs are known, only a moderate part of chemical space can be ...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.6b00391
更新日期:2016-12-27 00:00:00
abstract::Taking into account dynamical behavior and/or structural inaccuracies of receptor-ligand systems becomes increasingly important in structure-based drug design. Here, we describe the development of consensus Adaptation of Fields for Molecular Comparison (AFMoC) (abbreviated as AFMoCcon) models that account for multiple...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci7002472
更新日期:2007-11-01 00:00:00
abstract::The Common Instrument Middleware Architecture (CIMA) aims at Grid-enabling a wide range of scientific instruments and sensors to enable easy access to and sharing and storage of data produced by these instruments and sensors. This paper describes the implementation of CIMA applied to the field of single-crystal X-ray ...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci050368l
更新日期:2006-05-01 00:00:00
abstract::Visualizing high-dimensional data by projecting them into a two- or three-dimensional space is a popular approach in many scientific fields, including computer-aided drug design and cheminformatics. In contrast, dimensionality reduction techniques have been far less explored for materials informatics. Nevertheless, si...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.8b00552
更新日期:2018-12-24 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::In this work, we report an ab initio investigation based on density functional theory calculations within van der Waals D3 corrections to investigate the adsorption properties and activation of CO2 on transition-metal (TM) 13-atom clusters (TM = Ru, Rh, Pd, Ag), which is a key step for the development of subnano catal...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.9b00792
更新日期:2020-02-24 00:00:00
abstract::An ultrafast docking and virtual screening program, CRDOCK, is presented that contains (1) a search engine that can use a variety of sampling methods and an initial energy evaluation function, (2) several energy minimization algorithms for fine tuning the binding poses, and (3) different scoring functions. This modula...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci300194a
更新日期:2012-08-27 00:00:00
abstract::Structure-based computational target prediction methods identify potential targets for a bioactive compound. Methods based on protein-ligand docking so far face many challenges, where the greatest probably is the ranking of true targets in a large data set of protein structures. Currently, no standard data sets for ev...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci500131x
更新日期:2014-08-25 00:00:00
abstract::In this article, we present a systematic way to classify a family of high-genus fullerenes (HGFs) by decomposing them into two types of necklike structures, which are the negatively curved parts of parent toroidal carbon nanotubes. By replacing the faces of a uniform polyhedron with these necks, an HGF polyhedron corr...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci9001124
更新日期:2009-07-01 00:00:00
abstract::We have developed a computer program for molecular dynamics (MD) simulation that implements the Split Integration Symplectic Method (SISM) and is designed to run on specialized parallel computers. The MD integration is performed by the SISM, which analytically treats high-frequency vibrational motion and thus enables ...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci050216q
更新日期:2005-11-01 00:00:00
abstract::We propose an improved solvent contact model to estimate the solvation free energy of an organic molecule from individual atomic contributions. The modification of the solvation model involves the optimization of three kinds of parameters in the solvation free energy function: atomic fragmental volume, maximum atomic ...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci600453b
更新日期:2007-03-01 00:00:00
abstract::Novel statistical potentials derived from known protein structures are presented. They are designed to describe cation-pi and amino-pi interactions between a positively charged amino acid or an amino acid carrying a partially charged amino group and an aromatic moiety. These potentials are based on the propensity of r...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci050395b
更新日期:2006-03-01 00:00:00
abstract::The momentum gained by research on biologics has not been met yet with equal thrust on the informatics side. There is a noticeable lack of software for data management that empowers the bench scientists working on the development of biologic therapeutics. SARvision|Biologics is a tool to analyze data associated with b...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci400333x
更新日期:2013-10-28 00:00:00
abstract::QSPR studies, using scores of SciTegic's extended connectivity fingerprint as raw descriptors, were extended to the prediction of melting points and aqueous solubility of organic compounds. Robust partial least-squares models were developed that perform as well as the best published QSPR models for structurally divers...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci800024c
更新日期:2008-05-01 00:00:00
abstract::The yeast protein GCN4 is a transcriptional activator in the basic leucine zipper (bZip) family, whose distinguishing feature is the "chopstick-like" homodimer of alpha helices formed at the DNA-binding interface. While experiments have shown that truncated versions of the protein retain biologically relevant DNA-bind...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci500448e
更新日期:2014-10-27 00:00:00
abstract::The worldwide increase and proliferation of drug resistant microbes, coupled with the lag in new drug development, represents a major threat to human health. In order to reduce the time and cost for exploring the chemical search space, drug discovery increasingly relies on computational biology approaches. One key ste...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.0c00075
更新日期:2020-06-22 00:00:00
abstract::Deep learning has demonstrated significant potential in advancing state of the art in many problem domains, especially those benefiting from automated feature extraction. Yet, the methodology has seen limited adoption in the field of ligand-based virtual screening (LBVS) as traditional approaches typically require lar...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.0c00622
更新日期:2020-10-26 00:00:00
abstract::Saturated acyclic alkanes show steric strain if they are highly branched and, in extreme cases, fall apart rapidly at room temperature. Consequently, attempts to count the number of isomeric forms for a given molecular formula that neglect this physical consideration will inevitably overestimate the size of the availa...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci700246b
更新日期:2007-11-01 00:00:00
abstract::LEAFY (LFY) is a plant-specific transcription factor, with a variety of roles in different species. LFY contains a conserved DNA-binding domain (DBD) that determines its DNA-binding specificity. Recently, the structures of the dimeric LFY-DBD bound to different DNA motifs were successively solved by X-ray crystallogra...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci500705j
更新日期:2015-04-27 00:00:00
abstract::The enzyme UDP-galactopyranose mutase (UGM) represents a promising drug target for the treatment of infections with Trypanosoma cruzi. We have computed the Potential of Mean Force for the release of UDP-galactopyranose from UGM, using Umbrella Sampling simulations. The simulations revealed the conformational changes t...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.8b00675
更新日期:2019-02-25 00:00:00
abstract::Reaction classification has important applications, and many approaches to classification have been applied. Our own algorithm tests all maximum common substructures (MCS) between all reactant and product molecules in order to find an atom mapping containing the minimum chemical distance (MCD). Recent publications hav...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci400442f
更新日期:2013-11-25 00:00:00
abstract::The homodimeric catabolite activator protein (CAP) regulates the transcription of several bacterial genes based on the cellular concentration of cyclic adenosine monophosphate (cAMP). The binding of cAMP to CAP triggers allosteric communication between the cAMP binding domains (CBD) and DNA binding domains (DBD) of CA...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.0c00617
更新日期:2020-12-28 00:00:00
abstract::Resonance structures of polycyclic aromatic hydrocarbons can be associated with numerical formulas by assigning pi-electrons of C=C double bonds to individual benzenoid rings. Each C=C double bond in a resonance structure assigns two pi-electrons to a ring in a fused-benzenoid system if it is not shared by adjacent ri...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci050196s
更新日期:2006-01-01 00:00:00
abstract::The protonation states for nucleic acid bases are difficult to assess experimentally. In the context of DNA triplex, the protonation state of cytidine in the third strand is particularly important, because it needs to be protonated in order to form Hoogsteen hydrogen bonds. A sugar modification, locked nucleic acid (L...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.7b00741
更新日期:2018-04-23 00:00:00
abstract::Optimization of ligand binding affinity to the target protein of interest is a primary objective in small-molecule drug discovery. Until now, the prediction of binding affinities by computational methods has not been widely applied in the drug discovery process, mainly because of its lack of accuracy and reproducibili...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.6b00780
更新日期:2017-04-24 00:00:00
abstract::We present a succession of structural changes involved in hormone peptide activation of a prototypical GPCR. Microsecond molecular dynamics simulation generated conformational ensembles reveal propagation of structural changes through key "microswitches" within human AT1R bound to native hormone. The endocrine octa-pe...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.8b00583
更新日期:2019-01-28 00:00:00