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 crystallography. In this article, molecular dynamics (MD) simulations are employed to study two crystal structures of DNA-bound LFY protein from angiosperms and the moss Physcomitrella patens, respectively. The comparison of stabilities of the two systems is consistent with the experimental data of binding affinities. The calculation of hydrogen bonds showed that position 312 in LFY determines the difference of DNA-binding specificity. By using principal component analysis (PCA) and free energy landscape (FEL) methods, the open-close conformational change of the dimerization interface was found to be important for the system stability. At the dimerization interface, the protein-protein interaction has multiple influences on the cooperative DNA binding of LFY. The following analysis of DNA structural parameters further revealed that the protein-protein interaction contributes varying roles according to the specific DNA-binding efficiency. We propose that the protein-protein interaction serves a dual function as a connector between LFY monomers and a regulator of DNA-binding specificity. It will improve the robustness and adaptivity of the LFY-DNA ternary structure. This study provides some new insights into the understanding of the dynamics and interaction mechanism of dimeric LFY-DBD bound to DNA at the atomic level.
journal_name
J Chem Inf Modeljournal_title
Journal of chemical information and modelingauthors
Wan H,Chang S,Hu JP,Tian YX,Tian XHdoi
10.1021/ci500705jsubject
Has Abstractpub_date
2015-04-27 00:00:00pages
784-94issue
4eissn
1549-9596issn
1549-960Xjournal_volume
55pub_type
杂志文章abstract：:The anatomical therapeutic chemical (ATC) classification system maintained by the World Health Organization provides a global standard for the classification of medical substances and serves as a source for drug repurposing research. Nevertheless, it lacks several drugs that are major players in the global drug market...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci9000844
更新日期：2009-08-01 00:00:00
abstract：:Machine learning (ML) algorithms are gaining importance in the processing of chemical information and modeling of chemical reactivity problems. In this work, we have developed a perturbation-theory and machine learning (PTML) model combining perturbation theory (PT) and ML algorithms for predicting the yield of a give...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.8b00286
更新日期：2018-07-23 00:00:00
abstract：:Development of accurate force field parameters for molecular ions in the context of a polarizable energy function based on the classical Drude oscillator is a crucial step toward an accurate polarizable model for modeling and simulations of biological macromolecules. Toward this goal we have undertaken a hierarchical ...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.8b00132
更新日期：2018-05-29 00:00:00
abstract：:Interfacial hydration strongly influences interactions between biomolecules. For example, drug-target complexes are often stabilized by hydration networks formed between hydrophilic residues and water molecules at the interface. Exhaustive exploration of hydration networks is challenging for experimental as well as th...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.5b00638
更新日期：2016-01-25 00:00:00
abstract：:The human androgen receptor (AR) is a ligand-activated transcription factor that plays a pivotal role in the development and progression of prostate cancer (PCa). Many forms of castration-resistant prostate cancer (CRPC) still rely on the AR for survival. Currently used antiandrogens face clinical limitations as drug ...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.6b00400
更新日期：2016-12-27 00:00:00
abstract：:A new web portal for the CHARMM macromolecular modeling package, CHARMMing (CHARMM interface and graphics, http://www.charmming.org), is presented. This tool provides a user-friendly interface for the preparation, submission, monitoring, and visualization of molecular simulations (i.e., energy minimization, solvation,...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci800133b
更新日期：2008-09-01 00:00:00
abstract：:Protein-ligand binding is essential to almost all life processes. The understanding of protein-ligand interactions is fundamentally important to rational drug and protein design. Based on large scale data sets, we show that protein rigidity strengthening or flexibility reduction is a mechanism in protein-ligand bindin...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.7b00226
更新日期：2017-07-24 00:00:00
abstract：:This paper introduces the concept of an isomer network based on the reaction step counts between pairs of isomers as an alternative means to view and analyze isomer space. The computation of isomer networks is computationally expensive with respect to both run time and memory. Accordingly, this paper focuses on the de...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci4005173
更新日期：2014-01-27 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：:Membrane fusion, a key step in the early stages of virus propagation, allows the release of the viral genome in the host cell cytoplasm. The process is initiated by fusion peptides that are small, hydrophobic components of viral membrane-embedded glycoproteins and are typically conserved within virus families. Here, w...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.0c01231
更新日期：2021-01-25 00:00:00
abstract：:Human telomeric DNA G-quadruplex has been identified as a good therapeutic target in cancer treatment. G-quadruplex-specific ligands that stabilize the G-quadruplex have great potential to be developed as anticancer agents. Two crystal structures (an apo form of parallel stranded human telomeric G-quadruplex and its h...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.7b00287
更新日期：2017-11-27 00:00:00
abstract：:A three-dimensional homology model of the human histamine H 4 receptor was developed to investigate the binding mode of a series of structurally diverse H 4-agonists, i.e. histamine, clozapine, and the recently described selective, nonimidazole agonist VUF 8430. Mutagenesis studies and docking of these ligands in a rh...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci700474a
更新日期：2008-07-01 00:00:00
abstract：:Blockade of human ether-à-go-go related gene (hERG) channel prolongs the duration of the cardiac action potential and is a common reason for drug failure in preclinical safety trials. Therefore, it is of great importance to develop robust in silico tools to predict potential hERG blockers in the early stages of drug d...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci200271d
更新日期：2011-11-28 00:00:00
abstract：:In structure-based drug design, scoring functions are often employed to evaluate protein-ligand interactions. A variety of scoring functions have been developed so far, and thus, some objective benchmarks are desired for assessing their strength and weakness. The comparative assessment of scoring functions (CASF) benc...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.8b00545
更新日期：2019-02-25 00:00:00
abstract：:Reversible covalent inhibitors have drawn increasing attention in drug design, as they are likely more potent than noncovalent inhibitors and less toxic than covalent inhibitors. Despite those advantages, the computational prediction of reversible covalent binding presents a formidable challenge because the binding pr...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.8b00959
更新日期：2019-05-28 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：:The current drug virtual screen (VS) methods mainly include two categories. i.e., ligand/target structure-based virtual screen and that, utilizing protein-ligand interaction fingerprint information based on the large number of complex structures. Since the former one focuses on the one-side information while the later...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci200481c
更新日期：2012-03-26 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 balance between structural stability and functional plasticity in proteins that share common three-dimensional folds is the key factor that drives protein evolvability. The ability to distinguish the parts of homologous proteins that underlie common structural organization patterns from the parts acting as regulat...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.6b00504
更新日期：2017-04-24 00:00:00
abstract：:Traditionally, a drug potency is expressed in terms of thermodynamic quantities, mostly Kd, and empirical IC50 values. Although binding affinity as an estimate of drug activity remains relevant, it is increasingly clear that it is also important to include (un)binding kinetic parameters in the characterization of pote...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.8b00518
更新日期：2018-11-26 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：:This paper is an overview of the most significant and impactful interpretation approaches of quantitative structure-activity relationship (QSAR) models, their development, and application. The evolution of the interpretation paradigm from "model → descriptors → (structure)" to "model → structure" is indicated. The lat...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章,评审
doi：10.1021/acs.jcim.7b00274
更新日期：2017-11-27 00:00:00
abstract：:Small molecule flexible alignment is a critical component of both ligand- and structure-based methods in computer-aided drug discovery. Despite its importance, the availability of high-quality flexible alignment software packages is limited. Here, we present BCL::MolAlign, a freely available property-based molecular a...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.9b00020
更新日期：2019-02-25 00:00:00
abstract：:Rotational Profiler provides an analytical algorithm to compute sets of classical torsional dihedral parameters by fitting an empirical energy profile to a reference one that can be obtained experimentally or by quantum-mechanical methods. The resulting profiles are compatible with the functional forms in the most wid...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.0c01168
更新日期：2020-12-28 00:00:00
abstract：:In this work we present the third generation of FAst MEtabolizer (FAME 3), a collection of extra trees classifiers for the prediction of sites of metabolism (SoMs) in small molecules such as drugs, druglike compounds, natural products, agrochemicals, and cosmetics. FAME 3 was derived from the MetaQSAR database ( Pedre...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.9b00376
更新日期：2019-08-26 00:00:00
abstract：:We present a theoretical study on the performance of ensemble docking methodologies considering multiple protein structures. We perform a theoretical analysis of pose prediction experiments which is completely unbiased, as we make no assumptions about specific scoring functions, search paradigms, protein structures, o...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci2002796
更新日期：2011-11-28 00:00:00
abstract：:The integration of ligand- and structure-based strategies might sensitively increase the success of drug discovery process. We have recently described the application of Molecular Electrostatic Potential autocorrelated vectors (autoMEPs) in generating both linear (Partial Least-Square, PLS) and nonlinear (Response Sur...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci700300w
更新日期：2008-02-01 00:00:00
abstract：:In this study, in order to elucidate the action mechanism of traditional Chinese medicines (TCMs) that exhibit clinical efficacy for type II diabetes mellitus (T2DM), an integrated protocol that combines molecular docking and pharmacophore mapping was employed to find the potential inhibitors from TCM for the T2DM-rel...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci400146u
更新日期：2013-07-22 00:00:00
abstract：:Support vector regression (SVR) is a premier approach for the prediction of compound potency. Given the conceptual link between support vector machine (SVM) and SVR modeling, SVR is capable of accounting for continuous and discontinuous structure-activity relationships (SARs) in potency prediction, which further exten...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.8b00584
更新日期：2019-03-25 00:00:00
abstract：:The evaluation of regression QSAR model performance, in fitting, robustness, and external prediction, is of pivotal importance. Over the past decade, different external validation parameters have been proposed: Q(F1)(2), Q(F2)(2), Q(F3)(2), r(m)(2), and the Golbraikh-Tropsha method. Recently, the concordance correlati...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci300084j
更新日期：2012-08-27 00:00:00
