The VSGB 2.0 model: A next generation energy model for high resolution protein structure modeling
TLDR
Given the precision and robustness of the calculations, it is believed that the VSGB 2.0 model is suitable to tackle “real” problems, such as biological function modeling and structure‐based drug discovery.Abstract:
A novel energy model (VSGB 2.0) for high resolution protein structure modeling is described, which features an optimized implicit solvent model as well as physics-based corrections for hydrogen bonding, π-π interactions, self-contact interactions and hydrophobic interactions. Parameters of the VSGB 2.0 model were fit to a crystallographic database of 2239 single side chain and 100 11–13 residue loop predictions. Combined with an advanced method of sampling and a robust algorithm for protonation state assignment, the VSGB 2.0 model was validated by predicting 115 super long loops up to 20 residues. Despite the dramatically increasing difficulty in reconstructing longer loops, a high accuracy was achieved: all of the lowest energy conformations have global backbone RMSDs better than 2.0 A from the native conformations. Average global backbone RMSDs of the predictions are 0.51, 0.63, 0.70, 0.62, 0.80, 1.41, and 1.59 A for 14, 15, 16, 17, 18, 19, and 20 residue loop predictions, respectively. When these results are corrected for possible statistical bias as explained in the text, the average global backbone RMSDs are 0.61, 0.71, 0.86, 0.62, 1.06, 1.67, and 1.59 A. Given the precision and robustness of the calculations, we believe that the VSGB 2.0 model is suitable to tackle “real” problems, such as biological function modeling and structure-based drug discovery.read more
Citations
More filters
Journal ArticleDOI
Harnessing natural-product-inspired combinatorial chemistry and computation-guided synthesis to develop N-glycan modulators as anticancer agents
Wei-An Chen,Yu Hsin Chen,C. Y. Hsieh,Pi-Fang Hung,Chiao-Wen Chen,Chung-Hwan Chen,Jung Lee Lin,Ting-Jen R. Cheng,Tsui-Ling Hsu,Ying-Ta Wu,Chia-Ning Shen,Wei Chen +11 more
TL;DR: The synthesis and screening of a small library of novel bicyclic iminosugar-based scaffolds, prepared via natural product-inspired combinatorial chemistry (NPICC), resulted in the identification of a primaryα-hGMII inhibitor with 13.5-fold selectivity over α-hLM and its encouraging anti-HCC activity, without evidence of oligomannose accumulation.
Journal ArticleDOI
Structure of a 28.5 kDa duplex-embedded G-quadruplex system resolved to 7.4 Å resolution with cryo-EM
TL;DR: In this paper , the structure and dynamics of a 28.5 kDa duplex-G4-duplex (DGD) model system using cryo-EM, molecular dynamics, and small-angle X-ray scattering (SAXS) studies are reported.
Journal ArticleDOI
Identification of 1H-purine-2,6-dione derivative as a potential SARS-CoV-2 main protease inhibitor: molecular docking, dynamic simulations, and energy calculations
TL;DR: Using a test set of recently identified COVID-19 inhibitors, a pharmacophore was developed to screen 20 million drug-like compounds obtained from a freely accessible Zinc database, revealing compound 1 to be a promising SARS-Cov-2 MPro inhibitor suitable for further development.
Journal ArticleDOI
Estrogen receptor modulation of some polyphenols extracted from Daucus carota as a probable mechanism for antifertility effect: An in silico study
TL;DR: The seeds of Daucus carota, traditionally used by women in many countries to prevent conception, were proved to have negative impact on reproductive hormone levels as well as on the estrous cycles as mentioned in this paper.
Journal ArticleDOI
Molecular docking and oxidation kinetics of 3-phenyl coumarin derivatives by human CYP2A13
Risto O. Juvonen,Elmeri M. Jokinen,Juhani Huuskonen,Olli Kärkkäinen,Hannu Raunio,Olli T. Pentikäinen,Olli T. Pentikäinen +6 more
TL;DR: In this paper, the active site of CYP2A13 accepted more diversified types of coumarin substrates than the hepatic CYP 2A6 enzyme, and they found that 6-chloro or 6-methoxy and 3-hydroxyphenyl substituents increased affinity to the enzyme.
References
More filters
Journal ArticleDOI
Comparative Protein Modelling by Satisfaction of Spatial Restraints
Andrej Sali,Tom L. Blundell +1 more
TL;DR: A comparative protein modelling method designed to find the most probable structure for a sequence given its alignment with related structures, which is automated and illustrated by the modelling of trypsin from two other serine proteinases.
Journal ArticleDOI
SWISS-MODEL: an automated protein homology-modeling server
TL;DR: The SWISS-MODEL server is under constant development to improve the successful implementation of expert knowledge into an easy-to-use server.
Journal ArticleDOI
Semianalytical treatment of solvation for molecular mechanics and dynamics
TL;DR: In this paper, it was shown that the active carbon incorporation catalyst is carbided iron and this conclusion was well supported by bulk carbon to iron stoichiometries of 0.1-0.25 estimated from the TPHT peak areas which were adequate to represent 40-60'36 conversion to bulk carbides such as Fe,C or FeSC2.
Journal ArticleDOI
Improved protein-ligand docking using GOLD.
Marcel L. Verdonk,Jason C. Cole,Michael J. Hartshorn,Christopher W. Murray,Richard D. Taylor +4 more
TL;DR: In terms of producing binding energy estimates, the Goldscore function appears to perform better than the Chemscore function and the two consensus protocols, particularly for faster search settings.
Journal ArticleDOI
Funnels, pathways, and the energy landscape of protein folding: A synthesis
TL;DR: The work unifies several previously proposed ideas concerning the mechanism protein folding and delimits the regions of validity of these ideas under different thermodynamic conditions.