Abstract:
:Side-chain modeling is critical for protein structure prediction since the uniqueness of the protein structure is largely determined by its side-chain packing conformation. In this paper, differing from most approaches that rely on rotamer library sampling, we first propose a novel side-chain rotamer prediction method based on deep neural networks, named OPUS-RotaNN. Then, on the basis of our previous work OPUS-Rota2, we propose an open-source side-chain modeling framework, OPUS-Rota3, which integrates the results of different methods into its rotamer library as the sampling candidates. By including OPUS-RotaNN into OPUS-Rota3, we conduct our experiments on three native backbone test sets and one non-native backbone test set. On the native backbone test set, CAMEO-Hard61 for example, OPUS-Rota3 successfully predicts 51.14% of all side-chain dihedral angles with a tolerance criterion of 20° and outperforms OSCAR-star (50.87%), SCWRL4 (50.40%), and FASPR (49.85%). On the non-native backbone test set DB379-ITASSER, the accuracy of OPUS-Rota3 is 52.49%, better than OSCAR-star (48.95%), FASPR (48.69%), and SCWRL4 (48.29%). All the source codes including the training codes and the data we used are available at https://github.com/thuxugang/opus_rota3.
journal_name
J Chem Inf Modeljournal_title
Journal of chemical information and modelingauthors
Xu G,Wang Q,Ma Jdoi
10.1021/acs.jcim.0c00951subject
Has Abstractpub_date
2020-12-28 00:00:00pages
6691-6697issue
12eissn
1549-9596issn
1549-960Xjournal_volume
60pub_type
杂志文章abstract::Dynamical properties of proteins play an essential role in their function exertion. The elastic network model (ENM) is an effective and efficient tool in characterizing the intrinsic dynamical properties encoded in biomacromolecule structures. The Gaussian network model (GNM) and anisotropic network model (ANM) are th...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.0c01178
更新日期:2021-01-26 00:00:00
abstract::An important issue in developing protein-ligand docking methods is how to incorporate receptor flexibility. Consideration of receptor flexibility using an ensemble of precompiled receptor conformations or by employing an effectively enlarged binding pocket has been reported to be useful. However, direct consideration ...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci300342z
更新日期:2012-12-21 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::There is a growing public concern about the lack of reproducibility of experimental data published in peer-reviewed scientific literature. Herein, we review the most recent alerts regarding experimental data quality and discuss initiatives taken thus far to address this problem, especially in the area of chemical geno...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章,评审
doi:10.1021/acs.jcim.6b00129
更新日期:2016-07-25 00:00:00
abstract::Double-stranded DNA (dsDNA) has been established as an efficient medium for charge migration, bringing it to the forefront of the field of molecular electronics and biological research. The charge migration rate is controlled by the electronic couplings between the two nucleobases of DNA/RNA. These electronic coupling...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.0c01072
更新日期:2021-01-25 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::The more that is known about human and other genome sequences and the correlation between gene expression and the course of a disease, the more evident it seems to be that DNA is chosen as a drug target instead of proteins which are built with the information encoded by DNA. According to this approach, small minor gro...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci600500v
更新日期:2007-07-01 00:00:00
abstract::Calcium is involved in important intracellular processes, such as intracellular signaling from cell membrane receptors to the nucleus. Typically, calcium levels are kept at less than 100 nM in the nucleus and cytosol, but some calcium is stored in the endoplasmic reticulum (ER) lumen for rapid release to activate intr...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.6b00475
更新日期:2017-02-27 00:00:00
abstract::Reversible and irreversible covalent ligands are advanced cysteine protease inhibitors in the drug development pipeline. K777 is an irreversible inhibitor of cruzain, a necessary enzyme for the survival of the Trypanosoma cruzi (T. cruzi) parasite, the causative agent of Chagas disease. Despite their importance, irrev...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.9b01138
更新日期:2020-03-23 00:00:00
abstract::We describe here our tool named PyPLIF HIPPOS, which was newly developed to analyze the docking results of AutoDock Vina and PLANTS. Its predecessor, PyPLIF (https://github.com/radifar/pyplif), is a molecular interaction fingerprinting tool for the docking results of PLANTS, exclusively. Unlike its predecessor, PyPLIF...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.0c00305
更新日期:2020-08-24 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::Compounds with high-confidence target annotations and activity measurements in the original and current release of the ChEMBL database have been compared to better understand how the growth of compound activity data might influence the spectrum of ligand-target interactions and the degree of target promiscuity among a...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci3003304
更新日期:2012-10-22 00:00:00
abstract::The important role of water molecules in protein-ligand binding energetics has attracted wide attention in recent years. A range of computational methods has been developed to predict the favorable locations of water molecules in a protein binding pocket. Most of the current methods are based on extensive molecular dy...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.9b00619
更新日期:2020-09-28 00:00:00
abstract::On the order of hundreds of absorption, distribution, metabolism, excretion, and toxicity (ADME/Tox) models have been described in the literature in the past decade which are more often than not inaccessible to anyone but their authors. Public accessibility is also an issue with computational models for bioactivity, a...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.5b00143
更新日期:2015-06-22 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::The consistent handling of molecules is probably the most basic and important requirement in the field of cheminformatics. Reliable results can only be obtained if the underlying calculations are independent of the specific way molecules are represented in the input data. However, ensuring consistency is a complex tas...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci400724v
更新日期:2014-03-24 00:00:00
abstract::Great attention has been paid to the clinical significance of phosphodiesterase 5 (PDE5) inhibitors, such as sildenafil, tadalafil, and vardenafil widely used for erectile dysfunction. However, sildenafil causes side effects on visual functions since it shows similar potencies to inhibit PDE5 and PDE6, whereas tadalaf...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci400458z
更新日期:2013-11-25 00:00:00
abstract::While critically reviewing the current status of what is known about C28H14 and C30H14 benzenoid isomers, which are ubiquitous pyrolytic constituents, some new insights will be presented. Representative isomers belonging to these benzenoid hydrocarbons are at the crossroads to homologous series that extend to infinite...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci050298i
更新日期:2006-03-01 00:00:00
abstract::Following the theoretical model by Hann et al. moderately complex structures are preferable lead compounds since they lead to specific binding events involving the complete ligand molecule. To make this concept usable in practice for library design, we studied several complexity measures on the biological activity of ...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci0503558
更新日期:2006-03-01 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::The second extracellular loops (ECL2s) of G-protein-coupled receptors (GPCRs) are often involved in GPCR functions, and their structures have important implications in drug discovery. However, structure prediction of ECL2 is difficult because of its long length and the structural diversity among different GPCRs. In th...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.8b00148
更新日期:2018-06-25 00:00:00
abstract::Water is the natural medium of molecules in the cell and plays an important role in protein structure, function and interaction with small molecule ligands. However, the widely used molecular mechanics Poisson-Boltzmann surface area (MM/PBSA) method for binding energy calculation does not explicitly take account of wa...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci4001794
更新日期:2014-02-24 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::Retrieving molecules with specific structural features is a fundamental requirement of today's molecular database technologies. Estimates claim the chemical space relevant for drug discovery to be around 10⁶⁰ molecules. This figure is many orders of magnitude larger than the amount of molecules conventional databases ...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci400107k
更新日期:2013-07-22 00:00:00
abstract::A phenotypic screen (PS) is used to identify compounds causing a desired phenotype in a complex biological system where mechanisms and targets are largely unknown. Deconvoluting the mechanism of action of actives and identification of relevant targets and pathways remains a formidable challenge. Current methods fail t...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci400245c
更新日期:2014-02-24 00:00:00
abstract::Ab initio quantum-chemistry programs produce and use large amounts of data, which are usually stored on disk in the form of binary files. A FORTRAN library, named Q5Cost, has been designed and implemented in order to allow the storage of these data sets in a special data format built with the HDF5 technology. This dat...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci7000567
更新日期:2007-05-01 00:00:00
abstract::Protein dynamics play a critical role in ligand binding, and different models have been proposed to explain the relationships between protein motion and molecular recognition. Here, we present a study of ligand-binding processes associated with large conformational changes of a protein to elucidate the critical choice...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.7b00125
更新日期:2017-07-24 00:00:00
abstract::Serotonin 5-HT6 receptor antagonists are thought to play an important role in the treatment of psychiatry, Alzheimer's disease, and probably obesity. To find novel and potent 5-HT6 antagonists and to provide a new idea for drug design, we used a ligand-based pharmacophore to perform the virtual screening of a commerci...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci700160t
更新日期:2008-01-01 00:00:00
abstract::Chemical structure extraction from documents remains a hard problem because of both false positive identification of structures during segmentation and errors in the predicted structures. Current approaches rely on handcrafted rules and subroutines that perform reasonably well generally but still routinely encounter s...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.8b00669
更新日期:2019-03-25 00:00:00
abstract::The conformational properties of AT1 antagonist valsartan have been analyzed both in solution and at the binding site of the receptor. Low energy conformations of valsartan in solution were explored by NMR spectroscopy and molecular modeling studies. The NMR results showed the existence of two distinct and almost isoe...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci800427s
更新日期:2009-03-01 00:00:00