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
Loop prediction for a GPCR homology model: algorithms and results.
TL;DR: This is the first successful example of an RMSD validated, physics‐based loop prediction in the context of a GPCR homology model, and a new sampling algorithm that divides phase space into different regions, allowing more thorough sampling of long loops that greatly improves results.
Journal ArticleDOI
New insights into the cholesterol esterase- and lipase-inhibiting potential of bioactive peptides from camel whey hydrolysates: Identification, characterization, and molecular interaction.
TL;DR: In this paper, the antihypercholesterolemic bioactive peptides derived from peptic camel whey protein hydrolysates (CWPH) were generated at different time, temperature, and enzyme concentration.
Journal ArticleDOI
Targeting the NF-κB/IκBα complex via fragment-based E-Pharmacophore virtual screening and binary QSAR models.
TL;DR: The identification of new potent NF-κB/IκBα inhibitors may present a novel therapy for inflammation-mediated conditions as well as cancer, facilitating more efficient research, and leading the way to future drug development efforts.
Journal ArticleDOI
Structural assemblies of the di- and oligomeric G-protein coupled receptor TGR5 in live cells: an MFIS-FRET and integrative modelling study.
Annemarie Greife,Suren Felekyan,Qijun Ma,Christoph G. W. Gertzen,Lina Spomer,Mykola Dimura,Thomas Peulen,Christina Wöhler,Dieter Häussinger,Holger Gohlke,Verena Keitel,Claus A. M. Seidel +11 more
TL;DR: It is concluded that higher-order oligomers – likely with a tetramer organization - are formed from dimers, the smallest unit suggested for TGR5 Y111A variants.
Journal ArticleDOI
Insight into the LFA-1/SARS-CoV-2 Orf7a Complex by Protein-Protein Docking, Molecular Dynamics, and MM-GBSA Calculations.
TL;DR: In this article, a macromolecular assembly of the SARS-CoV-2 Orf7a structure has been studied, and protein-protein docking, molecular dynamics (MD) simulations, and a Molecular Mechanical-Generalized Born Surface Area (MM-GBSA)-based stage were enrolled to provide refined models.
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.