Abstract:
:Protein-protein interactions (PPIs) play vital roles in regulating biological processes, such as cellular and signaling pathways. Hotspots are certain residues located at protein-protein interfaces that contribute more in protein-protein binding than other residues. Research on the mutational effects of hotspots is important for understanding basic aspects of protein association. Hence, various computational tools have been developed to explore the impact of mutation hotspots, which will allow a better understanding of the forces that drive PPIs. However, tools that may provide comprehensive substitutions at hotspots are still rare. Hence, there is a strong need for a new free web server to explore mutational effects of hotspots. Herein we introduce a web server named PIIMS that integrates molecular dynamics simulation and one-step free energy perturbation. It contains two main computational functions: (1) computational alanine scanning analysis to identify hotspots and (2) full mutation scanning analysis to evaluate the effects of hotspot mutations. We rigidly validated its ability to predict binding free energy changes by using large and diverse datasets including 1,341 mutations from 50 PPIs with the correlation coefficient R = 0.75. The difference from the existing tools is that PIIMS can perform further evaluation of hotspot residues with regard to their different mutations. The PIIMS web server (accessible at http://chemyang.ccnu.edu.cn/ccb/server/PIIMS/index.php) is free and open to all users without login requirements.
journal_name
J Chem Inf Modeljournal_title
Journal of chemical information and modelingauthors
Wu FX,Yang JF,Mei LC,Wang F,Hao GF,Yang GFdoi
10.1021/acs.jcim.0c00966subject
Has Abstractpub_date
2021-01-25 00:00:00pages
14-20issue
1eissn
1549-9596issn
1549-960Xjournal_volume
61pub_type
杂志文章abstract::The accurate prediction of the adsorption energies of unsaturated molecules on graphene in the presence of water is essential for the design of molecules that can modify its properties and that can aid its processability. We here show that a semiempirical MO method corrected for dispersive interactions (PM6-DH2) can p...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci5003729
更新日期:2014-08-25 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::Throughout the drug discovery process, discovery teams are compelled to use statistics for making decisions using data from a variety of inputs. For instance, teams are asked to prioritize compounds for subsequent stages of the drug discovery process, given results from multiple screens. To assist in the prioritizatio...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci600556v
更新日期:2007-05-01 00:00:00
abstract::Databases of small, potentially bioactive molecules are ubiquitous across the industry and academia. Designed such that each unique compound should appear only once, the multiplicity of ways in which many compounds can be represented means that these databases require methods for standardizing the representation of ch...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.0c00232
更新日期:2020-08-24 00:00:00
abstract::The quantitative structure-activity relationship (QSAR) approach has been used to model a wide range of chemical-induced biological responses. However, it had not been utilized to model chemical-induced genomewide gene expression changes until very recently, owing to the complexity of training and evaluating a very la...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.7b00281
更新日期:2017-09-25 00:00:00
abstract::The modeling of nonlinear descriptor-target relationships is a topic of considerable interest in drug discovery. We, herein, continue reporting the use of the self-organizing map-a nonlinear, topology-preserving pattern recognition technique that exhibits considerable promise in modeling and decoding these relationshi...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci0500841
更新日期:2006-01-01 00:00:00
abstract::Maltose-binding protein is a periplasmic binding protein responsible for transport of maltooligosaccarides through the periplasmic space of Gram-negative bacteria, as a part of the ABC transport system. The molecular mechanisms of the initial ligand binding and induced large scale motion of the protein's domains still...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci500520q
更新日期:2015-02-23 00:00:00
abstract::G-protein coupled receptors (GPCRs) are highly relevant drug targets. Four GPCRs with known crystal structure were analyzed with docking (AutoDock4) and postdocking (MM-PBSA) in order to evaluate the ability to recognize known antagonists from a larger database of molecular decoys and to predict correct binding modes....
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci4000745
更新日期:2013-04-22 00:00:00
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::Selecting a small subset of descriptors from a large pool to build a predictive quantitative structure-activity relationship (QSAR) model is an important step in the QSAR modeling process. In general, subset selection is very hard to solve, even approximately, with guaranteed performance bounds. Traditional approaches...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci600563w
更新日期:2007-05-01 00:00:00
abstract::It is demonstrated that the fragmentation of druglike molecules by applying simplistic pseudo-retrosynthesis results in a stock of chemically meaningful building blocks for de novo molecule generation. A stochastic search algorithm in conjunction with ligand-based similarity scoring (Flux: fragment-based ligand builde...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci0503560
更新日期:2006-03-01 00:00:00
abstract::Our main objective was to compile a data set of high-quality protein-fragment complexes and make it publicly available. Once assembled, the data set was challenged using docking procedures to address the following questions: (i) Can molecular docking correctly reproduce the experimentally solved structures? (ii) How t...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci2003363
更新日期:2011-11-28 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::Iterative screening has emerged as a promising approach to increase the efficiency of high-throughput screening (HTS) campaigns in drug discovery. By learning from a subset of the compound library, inferences on what compounds to screen next can be made by predictive models. One of the challenges of iterative screenin...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.8b00724
更新日期:2019-03-25 00:00:00
abstract::Peptides that bind to ion channels have attracted much interest as potential lead molecules for the development of new drugs and insecticides. However, the structure determination of large peptide-channel complexes using experimental methods is challenging. Thus structural models are often derived from combining exper...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.5b00529
更新日期:2016-01-25 00:00:00
abstract::The in silico prediction of unwanted side effects (SEs) caused by the promiscuous behavior of drugs and their targets is highly relevant to the pharmaceutical industry. Considerable effort is now being put into computational and experimental screening of several suspected off-target proteins in the hope that SEs might...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.5b00120
更新日期:2015-09-28 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::Metabolic stability is an important property of drug molecules that should-optimally-be taken into account early on in the drug design process. Along with numerous medium- or high-throughput assays being implemented in early drug discovery, a prediction tool for this property could be of high value. However, metabolic...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci700142c
更新日期:2008-04-01 00:00:00
abstract::As a key player in cell adhesion, the glycoprotein fibronectin is involved in the complex mechanobiology of the extracellular matrix. Although the function of many modules in the fibronectin molecule has already been understood, the structure and biological relevance of the C-terminal cross-linked region (CTXL) still ...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.9b00555
更新日期:2019-10-28 00:00:00
abstract::Aminoglycosides are antibiotics targeting the 16S RNA A site of the bacterial ribosome. There have been many efforts directed toward design of their synthetic derivatives, however with only few successes. As RNA binders, aminoglycosides are also a difficult target for computational drug design, since most of the exist...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci800361a
更新日期:2009-02-01 00:00:00
abstract::Fragment-based methods have emerged in the last two decades as alternatives to traditional high throughput screenings for the identification of chemical starting points in drug discovery. One arguable yet popular assumption about fragment-based design is that the fragment binding mode remains conserved upon chemical e...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci300355p
更新日期:2012-12-21 00:00:00
abstract::The prediction of protein-ligand binding affinity has recently been improved remarkably by machine-learning-based scoring functions. For example, using a set of simple descriptors representing the atomic distance counts, the RF-Score improves the Pearson correlation coefficient to about 0.8 on the core set of the PDBb...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.7b00049
更新日期:2017-04-24 00:00:00
abstract::The roles of chemical compounds in biological systems are now systematically analyzed by high-throughput experimental technologies. To automate the processing and interpretation of large-scale data it is necessary to develop bioinformatics methods to extract information from the chemical structures of these small mole...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci700006f
更新日期:2007-07-01 00:00:00
abstract::Metal-ligand (M-L) bond lengths for a range of ligands (carboxylates, chlorides, pyridines, water, tertiary phosphines, and alkenes) and a variety of metals have been retrieved from the Cambridge Structural Database, CSD. Analysis of the factors which affect M-L bond lengths (for example, ligand coordination mode, oxi...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci0500785
更新日期:2005-11-01 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::We report a novel method called ADAN (Applicability Domain ANalysis) for assessing the reliability of drug property predictions obtained by in silico methods. The assessment provided by ADAN is based on the comparison of the query compound with the training set, using six diverse similarity criteria. For every criteri...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci500172z
更新日期:2014-05-27 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::Protein-polysaccharide complexes constructed via self-assembly methods are often used to develop novel biomaterials for a wide range of applications in biomedicine, food, and biotechnology. The objective of this work was to investigate theoretically and to demonstrate via constant-pH Monte Carlo simulations that the c...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.9b00814
更新日期:2020-02-24 00:00:00
abstract::G protein-coupled receptors (GPCRs) are the largest family of cell surface receptors, which is arguably the most important family of drug target. With the technology breakthroughs in X-ray crystallography and cryo-electron microscopy, more than 300 GPCR-ligand complex structures have been publicly reported since 2007,...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.9b00699
更新日期:2020-09-28 00:00:00
abstract::Accurate and affordable assessment of ligand-protein affinity for structure-based virtual screening (SB-VS) is a standing challenge. Hence, empirical postdocking filters making use of various types of structure-activity information may prove useful. Here, we introduce one such filter based upon three-dimensional struc...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci500319f
更新日期:2014-09-22 00:00:00